@article{wang_tzeng_huang_maguire_hoyo_allen_2023, title={Duration of exposure to epidural anesthesia at delivery, DNA methylation in umbilical cord blood and their association with offspring asthma in Non-Hispanic Black women}, volume={9}, ISSN={["2058-5888"]}, DOI={10.1093/eep/dvac026}, abstractNote={Abstract Epidural anesthesia is an effective pain relief modality, widely used for labor analgesia. Childhood asthma is one of the commonest chronic medical illnesses in the USA which places a significant burden on the health-care system. We recently demonstrated a negative association between the duration of epidural anesthesia and the development of childhood asthma; however, the underlying molecular mechanisms still remain unclear. In this study of 127 mother–child pairs comprised of 75 Non-Hispanic Black (NHB) and 52 Non-Hispanic White (NHW) from the Newborn Epigenetic Study, we tested the hypothesis that umbilical cord blood DNA methylation mediates the association between the duration of exposure to epidural anesthesia at delivery and the development of childhood asthma and whether this differed by race/ethnicity. In the mother–child pairs of NHB ancestry, the duration of exposure to epidural anesthesia was associated with a marginally lower risk of asthma (odds ratio = 0.88, 95% confidence interval = 0.76–1.01) for each 1-h increase in exposure to epidural anesthesia. Of the 20 CpGs in the NHB population showing the strongest mediation effect, 50% demonstrated an average mediation proportion of 52%, with directional consistency of direct and indirect effects. These top 20 CpGs mapped to 21 genes enriched for pathways engaged in antigen processing, antigen presentation, protein ubiquitination and regulatory networks related to the Major Histocompatibility Complex (MHC) class I complex and Nuclear Factor Kappa-B (NFkB) complex. Our findings suggest that DNA methylation in immune-related pathways contributes to the effects of the duration of exposure to epidural anesthesia on childhood asthma risk in NHB offspring.}, number={1}, journal={ENVIRONMENTAL EPIGENETICS}, author={Wang, Yaxu and Tzeng, Jung-Ying and Huang, Yueyang and Maguire, Rachel and Hoyo, Cathrine and Allen, Terrence K.}, year={2023}, month={Jan} }
 @article{sosnowski_ellison-barnes_kaufman_hoyo_murphy_hernandez_marchesoni_klein_johnson_2023, title={Financial stress as a mediator of the association between maternal childhood adversity and infant birth weight, gestational age, and NICU admission}, volume={23}, ISSN={["1471-2458"]}, DOI={10.1186/s12889-023-15495-0}, abstractNote={To examine whether financial stress during pregnancy mediates the association between maternal exposure to adverse childhood experiences (ACEs) and three birth outcomes (i.e., gestational age, birth weight, and admission to the neonatal intensive care unit [NICU]).Data were obtained from a prospective cohort study of pregnant women and their infants in Florida and North Carolina. Mothers (n = 531; Mage at delivery = 29.8 years; 38% Black; 22% Hispanic) self-reported their exposure to childhood adversity and financial stress during pregnancy. Data on infant gestational age at birth, birth weight, and admission to the NICU were obtained from medical records within 7 days of delivery. Mediation analysis was used to test study hypotheses, adjusting for study cohort, maternal race, ethnicity, body mass index, and tobacco use during pregnancy.There was evidence of an indirect association between maternal exposure to childhood adversity and infant gestational age at birth (b = -0.03, 95% CI = -0.06 - -0.01) and infant birth weight (b = -8.85, 95% CI = -18.60 - -1.28) such that higher maternal ACE score was associated with earlier gestational age and lower infant birth weight through increases in financial distress during pregnancy. There was no evidence of an indirect association between maternal exposure to childhood adversity and infant NICU admission (b = 0.01, 95% CI = -0.02-0.08).Findings demonstrate one pathway linking maternal childhood adversity to a potentially preterm birth or shorter gestational age, in addition to low birth weight at delivery, and present an opportunity for targeted intervention to support expecting mothers who face financial stress.}, number={1}, journal={BMC PUBLIC HEALTH}, author={Sosnowski, David W. W. and Ellison-Barnes, Alejandra and Kaufman, Joan and Hoyo, Cathrine and Murphy, Susan K. K. and Hernandez, Raquel G. G. and Marchesoni, Joddy and Klein, Lauren M. M. and Johnson, Sara B.}, year={2023}, month={Mar} }
 @article{sosnowski_ellison-barnes_kaufman_hoyo_murphy_hernandez_marchesoni_klein_johnson_2023, title={Financial stress as a mediator of the association between maternal childhood adversity and infant birth weight, gestational age, and NICU admission (vol 23, 606, 2023)}, volume={23}, ISSN={["1471-2458"]}, DOI={10.1186/s12889-023-15783-9}, number={1}, journal={BMC PUBLIC HEALTH}, author={Sosnowski, David W. and Ellison-Barnes, Alejandra and Kaufman, Joan and Hoyo, Cathrine and Murphy, Susan K. and Hernandez, Raquel G. and Marchesoni, Joddy and Klein, Lauren M. and Johnson, Sara B.}, year={2023}, month={May} }
 @article{fuemmeler_glasgow_schechter_maguire_sheng_bidopia_barsell_ksinan_zhang_lin_et al._2023, title={Prenatal and Childhood Smoke Exposure Associations with Cognition, Language, and Attention-Deficit/Hyperactivity Disorder}, volume={256}, ISSN={["1097-6833"]}, DOI={10.1016/j.jpeds.2022.11.041}, abstractNote={To assess the relationships of prenatal and childhood smoke exposure with specific neurodevelopmental and behavioral problems during early childhood.A subsample (n = 386) of mother-child dyads from the Newborn Epigenetic Study (NEST) prebirth cohort participated in the study. Cotinine concentrations were used to objectively measure prenatal and childhood smoke exposure when youth were aged 3-13 years. Multivariable regression models were used to estimate associations of prenatal and childhood cotinine concentrations with performance on the National Institutes of Health (NIH) Toolbox and attention-deficit/hyperactivity disorder and behavioral symptoms, measured using the Behavior Assessment System for Children, 2nd edition (BASC-2).After adjusting for confounders, childhood cotinine concentrations were associated with poorer cognitive performance on tasks measuring cognitive flexibility (B = -1.29; P = .03), episodic memory (B = -0.97; P = .02), receptive language development (B = -0.58; P = .01), and inhibitory control and attention (B = -1.59; P = .006). Although childhood cotinine concentration was associated with higher levels of attention problems (B = 0.83; P = .004) on the BASC-2, after adjustment for confounders, the association is nonsignificant. Although associations for maternal cotinine concentrations were null, an interaction was detected between prenatal and childhood cotinine concentrations on the NIH Toolbox Picture Vocabulary Task (P = .02).Our findings suggest that childhood tobacco smoke exposure may lead to poorer attention regulation and language acquisition, complex visual processing ability, and attention problems.}, journal={JOURNAL OF PEDIATRICS}, author={Fuemmeler, Bernard F. and Glasgow, Trevin E. and Schechter, Julia C. and Maguire, Rachel and Sheng, Yaou and Bidopia, Tatyana and Barsell, D. Jeremy and Ksinan, Albert and Zhang, Junfeng and Lin, Yan and et al.}, year={2023}, month={May}, pages={77-+} }
 @article{haight_maselko_ghastine_hoyo_martin_2023, title={Residential segregation and prenatal depression in a non-Hispanic Black and Hispanic cohort in North Carolina}, volume={83}, ISSN={["1873-2585"]}, DOI={10.1016/j.annepidem.2023.04.015}, abstractNote={Investigate residential segregation and prenatal depression in a non-Hispanic (NH) Black and Hispanic North Carolina pregnancy cohort. Demographics, prenatal depression (Center for Epidemiological Studies Depression scale ≥16), and residence from the 2006–2009 Newborn Epigenetic Survey were linked to Census-tract levels of racial and economic segregation (Index of Concentration at the Extremes) from the American Community Survey 2005–2009 5-year estimates. Adjusted prevalence ratios (aPR) for prenatal depression compared living in Index of Concentration at the Extremes tertiles 1 and 2 (higher proportion NH Black or Hispanic and/or low income) to 3 (higher proportion NH white and/or high-income), accounting for neighborhood clustering, age, education, employment, parity, and marital status. Among the 773 survey participants (482 NH Black and 291 Hispanic), 35.7% and 27.2% of NH Black and Hispanic participants had prenatal depression, respectively. For NH Black participants, depression prevalence was 17% lower for tertile 1 versus 3 for the NH Black/white (aPR=0.83; 95% CI=0.62–1.10), low/high income (aPR=0.83; 95% CI=0.62–1.11), and low-income NH Black/high-income NH white (aPR=0.82; 95% CI=0.61–1.09) measures. For Hispanic participants, estimates were weaker in the opposite direction for the Hispanic/NH white (aPR=1.02; 95% CI=0.71–1.47), low/high income (aPr=1.14; (95% CI=0.76–1.69), and low-income Hispanic/high-income NH white (aPR=1.12; 95% CI=0.78–1.60) measures. Residential segregation’s impact on prenatal depression may differ by race/ethnicity and level of segregation, but findings are imprecise due to small sample sizes. Longitudinal research spanning greater geographic areas is needed.}, journal={ANNALS OF EPIDEMIOLOGY}, author={Haight, Sarah C. and Maselko, Joanna and Ghastine, Lea and Hoyo, Cathrine and Martin, Chantel L.}, year={2023}, month={Jul}, pages={15–22} }
 @article{moylan_mavis_jima_maguire_bashir_hyun_cabezas_parish_niedzwiecki_diehl_et al._2022, title={Alterations in DNA methylation associate with fatty liver and metabolic abnormalities in a multi-ethnic cohort of pre-teenage children}, ISSN={["1559-2308"]}, DOI={10.1080/15592294.2022.2039850}, abstractNote={Non-Alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. Epigenetic alterations, such as through DNA methylation (DNAm), may link adverse childhood exposures and fatty liver and provide non-invasive methods for identifying children at high risk for NAFLD and associated metabolic dysfunction. We investigated the association between differential DNAm and liver fat content (LFC) and liver injury in pre-adolescent children. Leveraging data from the Newborn Epigenetics Study (NEST), we enrolled 90 mother-child dyads and used linear regression to identify CpG sites and differentially methylated regions (DMRs) in peripheral blood associated with LFC and alanine aminotransferase (ALT) levels in 7-12yo children. DNAm was measured using Infinium HumanMethylationEPIC BeadChips (Illumina). LFC and fibrosis were quantified by magnetic resonance imaging proton density fat fraction and elastography. Median LFC was 1.4% (range, 0.3-13.4%) and MRE was 2.5 kPa (range, 1.5-3.6kPa). Three children had LFC ≥ 5%, while six (7.6%) met our definition of NAFLD (LFC ≥ 3.7%). All children with NAFLD were obese and five were Black. LFC was associated with 88 DMRs and 106 CpGs (FDR<5%). The top two CpGs, cg25474373 and cg07264203, mapped to or near RFTN2 and PRICKLE2 genes. These two CpG sites were also significantly associated with a NAFLD diagnosis. As higher LFC associates with an adverse cardiometabolic profile already in childhood, altered DNAm may identify these children early in disease course for targeted intervention. Larger, longitudinal studies are needed to validate these findings and determine mechanistic relevance.}, journal={EPIGENETICS}, author={Moylan, Cynthia A. and Mavis, Alisha M. and Jima, Dereje and Maguire, Rachel and Bashir, Mustafa and Hyun, Jeongeun and Cabezas, Melanie N. and Parish, Alice and Niedzwiecki, Donna and Diehl, Anna Mae and et al.}, year={2022}, month={Feb} }
 @article{gonzalez-nahm_ostbye_hoyo_kravitz_benjamin-neelon_2022, title={Associations Among Food Security, Diet Quality, and Dietary Intake During Pregnancy in a Predominantly African American Group of Women from North Carolina}, volume={122}, ISSN={["2212-2680"]}, DOI={10.1016/j.j.2021.08.110}, number={3}, journal={JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS}, author={Gonzalez-Nahm, Sarah and Ostbye, Truls and Hoyo, Cathrine and Kravitz, Richard M. and Benjamin-Neelon, Sara E.}, year={2022}, month={Mar}, pages={565–572} }
 @article{lloyd_skinner_maguire_murphy_motsinger-reif_hoyo_house_2022, title={Clomifene and Assisted Reproductive Technology in Humans Are Associated with Sex-Specific Offspring Epigenetic Alterations in Imprinted Control Regions}, volume={23}, ISSN={["1422-0067"]}, url={https://doi.org/10.3390/ijms231810450}, DOI={10.3390/ijms231810450}, abstractNote={Children conceived with assisted reproductive technology (ART) have an increased risk of adverse outcomes, including congenital malformations and imprinted gene disorders. In a retrospective North Carolina-based-birth-cohort, we examined the effect of ovulation drugs and ART on CpG methylation in differentially methylated CpGs in known imprint control regions (ICRs). Nine ICRs containing 48 CpGs were assessed for methylation status by pyrosequencing in mixed leukocytes from cord blood. After restricting to non-smoking, college-educated participants who agreed to follow-up, ART-exposed (n = 27), clomifene-only-exposed (n = 22), and non-exposed (n = 516) groups were defined. Associations of clomifene and ART with ICR CpG methylation were assessed with linear regression and stratifying by offspring sex. In males, ART was associated with hypomethylation of the PEG3 ICR [β(95% CI) = -1.46 (-2.81, -0.12)] and hypermethylation of the MEG3 ICR [3.71 (0.01, 7.40)]; clomifene-only was associated with hypomethylation of the NNAT ICR [-5.25 (-10.12, -0.38)]. In female offspring, ART was associated with hypomethylation of the IGF2 ICR [-3.67 (-6.79, -0.55)]. Aberrant methylation of these ICRs has been associated with cardiovascular disease and metabolic and behavioral outcomes in children. The results suggest that the increased risk of adverse outcomes in offspring conceived through ART may be due in part to altered methylation of ICRs. Larger studies utilizing epigenome-wide interrogation are warranted.}, number={18}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, author={Lloyd, Dillon T. and Skinner, Harlyn G. and Maguire, Rachel and Murphy, Susan K. and Motsinger-Reif, Alison A. and Hoyo, Cathrine and House, John S.}, year={2022}, month={Sep} }
 @article{jima_skaar_planchart_motsinger-reif_cevik_park_cowley_wright_house_liu_et al._2022, title={Genomic map of candidate human imprint control regions: the imprintome}, volume={6}, ISSN={["1559-2308"]}, url={https://doi.org/10.1080/15592294.2022.2091815}, DOI={10.1080/15592294.2022.2091815}, abstractNote={Imprinted genes – critical for growth, metabolism, and neuronal function – are expressed from one parental allele. Parent-of-origin-dependent CpG methylation regulates this expression at imprint control regions (ICRs). Since ICRs are established before tissue specification, these methylation marks are similar across cell types. Thus, they are attractive for investigating the developmental origins of adult diseases using accessible tissues, but remain unknown. We determined genome-wide candidate ICRs in humans by performing whole-genome bisulphite sequencing (WGBS) of DNA derived from the three germ layers and from gametes. We identified 1,488 hemi-methylated candidate ICRs, including 19 of 25 previously characterized ICRs (https://humanicr.org/). Gamete methylation approached 0% or 100% in 332 ICRs (178 paternally and 154 maternally methylated), supporting parent-of-origin-specific methylation, and 65% were in well-described CTCF-binding or DNaseI hypersensitive regions. This draft of the human imprintome will allow for the systematic determination of the role of early-acquired imprinting dysregulation in the pathogenesis of human diseases and developmental and behavioural disorders.}, journal={EPIGENETICS}, author={Jima, Dereje D. and Skaar, David A. and Planchart, Antonio and Motsinger-Reif, Alison and Cevik, Sebnem E. and Park, Sarah S. and Cowley, Michael and Wright, Fred and House, John and Liu, Andy and et al.}, year={2022}, month={Jun} }
 @article{lodge_haji-noor_gutierrez_aiello_hoyo_emch_martin_2022, title={Gestational exposure to neighborhood police-reported crime and early childhood blood pressure in Durham, NC}, volume={75}, ISSN={["1873-2054"]}, DOI={10.1016/j.healthplace.2022.102800}, abstractNote={Gestational exposure to police-reported crime is associated with adverse birth outcomes, but no previous research has evaluated the effects of gestational crime exposure on early childhood health or attempted to disentangle the health effects of neighborhood crime from the effects of neighborhood policing. Using data from 672 Newborn Epigenetics Study participants, we evaluate the effects of gestational exposure to violent crime and racialized drug policing on early childhood blood pressure. We demonstrate that violence and drug policing are consistently associated with increased blood pressure among children born to Black participants but not White or Latinx participants.}, journal={HEALTH & PLACE}, author={Lodge, Evans K. and Haji-Noor, Zakiya and Gutierrez, Carmen M. and Aiello, Allison E. and Hoyo, Cathrine and Emch, Michael E. and Martin, Chantel L.}, year={2022}, month={May} }
 @article{gonzalez-nahm_marchesoni_maity_maguire_house_tucker_atkinson_murphy_hoyo_2022, title={Maternal Mediterranean Diet Adherence and Its Associations with Maternal Prenatal Stressors and Child Growth}, volume={6}, ISSN={["2475-2991"]}, DOI={10.1093/cdn/nzac146}, abstractNote={Psychosocial and physiologic stressors, such as depression and obesity, during pregnancy can have negative consequences, such as increased systemic inflammation, contributing to chronic disease for both mothers and their unborn children. These conditions disproportionately affect racial/ethnic minorities. The effects of recommended dietary patterns in mitigating the effects of these stressors remain understudied.We aimed to evaluate the relations between maternal Mediterranean diet adherence (MDA) and maternal and offspring outcomes during the first decade of life in African Americans, Hispanics, and Whites.This study included 929 mother-child dyads from the NEST (Newborn Epigenetics STudy), a prospective cohort study. FFQs were used to estimate MDA in pregnant women. Weight and height were measured in children between birth and age 8 y. Multivariable linear regression models were used to examine associations between maternal MDA, inflammatory cytokines, and pregnancy and postnatal outcomes.More than 55% of White women reported high MDA during the periconceptional period compared with 22% of Hispanic and 18% of African American women (P < 0.05). Higher MDA was associated with lower likelihood of depressive mood (β = -0.45; 95% CI: -0.90, -0.18; P = 0.02) and prepregnancy obesity (β = -0.29; 95% CI: -0.57, -0.0002; P = 0.05). Higher MDA was also associated with lower body size at birth, which was maintained to ages 3-5 and 6-8 y-this association was most apparent in White children (3-5 y: β = -2.9, P = 0.02; 6-8 y: β = -3.99, P = 0.01).If replicated in larger studies, our data suggest that MDA provides a potent avenue by which effects of prenatal stressors on maternal and fetal outcomes can be mitigated to reduce ethnic disparities in childhood obesity.}, number={11}, journal={CURRENT DEVELOPMENTS IN NUTRITION}, author={Gonzalez-Nahm, Sarah and Marchesoni, Joddy and Maity, Arnab and Maguire, Rachel L. and House, John S. and Tucker, Rachel and Atkinson, Tamara and Murphy, Susan K. and Hoyo, Cathrine}, year={2022}, month={Nov} }
 @article{joglekar_grenier_hoyo_hoffman_murphy_2022, title={Maternal tobacco smoke exposure is associated with increased DNA methylation at human metastable epialleles in infant cord blood}, volume={8}, ISSN={["2058-5888"]}, DOI={10.1093/eep/dvac005}, abstractNote={Metastable epialleles (MEs) are genomic regions that are stochastically methylated prior to germ layer specification and exhibit high interindividual but low intra-individual variability across tissues. ME methylation is vulnerable to environmental stressors, including diet. Tobacco smoke (TS) exposure during pregnancy is associated with adverse impacts on fetal health and maternal micronutrient levels as well as altered methylation. Our objective was to determine if maternal smoke exposure impacts methylation at MEs. Consistent with prior studies, we observed reductions in one-carbon pathway micronutrients with gestational TS exposure, including maternal folate (P = 0.02) and vitamins B6 (P = 0.05) and B12 (P = 0.007). We examined putative MEs BOLA3, PAX8, and ZFYVE28 in cord blood specimens from 85 Newborn Epigenetics STudy participants. Gestational TS exposure was associated with elevated DNA methylation at PAX8 (+5.22% average methylation; 95% CI: 0.33% to 10.10%; P = 0.037). In human conceptal kidney tissues, higher PAX8 transcription was associated with lower methylation (Rs = 0.55; P = 0.07), suggesting that the methylation levels established at MEs, and their environmentally induced perturbation, may have meaningful, tissue-specific functional consequences. This may be particularly important because PAX8 is implicated in several cancers, including pediatric kidney cancer. Our data are the first to indicate vulnerability of human ME methylation establishment to TS exposure, with a general trend of increasing levels of methylation at these loci. Further investigation is needed to determine how TS exposure-mediated changes in DNA methylation at MEs, and consequent expression levels, might affect smoking-related disease risk.}, number={1}, journal={ENVIRONMENTAL EPIGENETICS}, author={Joglekar, Rashmi and Grenier, Carole and Hoyo, Cathrine and Hoffman, Kate and Murphy, Susan K.}, year={2022}, month={Mar} }
 @misc{solomon_huen_yousefi_kupers_gonzalez_suderman_reese_page_gruzieva_rzehak_et al._2022, title={Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation}, volume={789}, ISSN={["1388-2139"]}, DOI={10.1016/j.mrrev.2022.108415}, abstractNote={Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits. We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5–10 years from 8 cohorts (n = 4268). In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p < 1.3 × 10−7) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (p < 1.1 × 10−6) in older children and had methylation differences in the same direction. This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes.}, journal={MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH}, author={Solomon, Olivia and Huen, Karen and Yousefi, Paul and Kupers, Leanne K. and Gonzalez, Juan R. and Suderman, Matthew and Reese, Sarah E. and Page, Christian M. and Gruzieva, Olena and Rzehak, Peter and et al.}, year={2022} }
 @article{wheeler_boyle_barsell_maguire_dahman_murphy_hoyo_zhang_oliver_mcclernon_et al._2022, title={Neighborhood Deprivation is Associated with Increased Risk of Prenatal Smoke Exposure}, ISSN={["1573-6695"]}, DOI={10.1007/s11121-022-01355-7}, abstractNote={Despite years of advisories against the behavior, smoking among pregnant women remains a persistent public health issue in the USA. Recent estimates suggest that 9.4% of women smoke before pregnancy and 7.1% during pregnancy in the USA. Epidemiological research has attempted to pinpoint individual-level and neighborhood-level factors for smoking during pregnancy, including educational attainment, employment status, housing conditions, poverty, and racial demographics. However, most of these studies have relied upon self-reported measures of smoking, which are subject to reporting bias. To more accurately and objectively assess smoke exposure in mothers during pregnancy, we used Bayesian index models to estimate a neighborhood deprivation index (NDI) for block groups in Durham County, North Carolina, and its association with cotinine, a marker of smoke exposure, in pregnant mothers (n = 887 enrolled 2005-2011). Results showed a significant positive association between NDI and log cotinine (beta = 0.20, 95% credible interval = [0.11, 0.29]) after adjusting for individual covariates (e.g., race/ethnicity and education). The two most important variables in the NDI according to the estimated index weights were percent females without a high school degree and percent Black population. At the individual level, Hispanic and other race/ethnicity were associated with lowered cotinine compared with non-Hispanic Whites. Higher education levels were also associated with lowered cotinine. In summary, our findings provide stronger evidence that the socio-geographic variables of educational attainment and neighborhood racial composition are important factors for smoking and secondhand smoke exposure during pregnancy and can be used to target intervention efforts.}, journal={PREVENTION SCIENCE}, author={Wheeler, David C. and Boyle, Joseph and Barsell, D. Jeremy and Maguire, Rachel L. and Dahman, Bassam and Murphy, Susan K. and Hoyo, Cathrine and Zhang, Jim and Oliver, Jason A. and McClernon, Joseph and et al.}, year={2022}, month={Feb} }
 @misc{vidal_moylan_wilder_grant_murphy_hoyo_2022, title={Racial disparities in liver cancer: Evidence for a role of environmental contaminants and the epigenome}, volume={12}, ISSN={["2234-943X"]}, DOI={10.3389/fonc.2022.959852}, abstractNote={Liver cancer incidence has tripled since the early 1980s, making this disease one of the fastest rising types of cancer and the third leading cause of cancer-related deaths worldwide. In the US, incidence varies by geographic location and race, with the highest incidence in the southwestern and southeastern states and among racial minorities such as Hispanic and Black individuals. Prognosis is also poorer among these populations. The observed ethnic disparities do not fully reflect differences in the prevalence of risk factors, e.g., for cirrhosis that may progress to liver cancer or from genetic predisposition. Likely substantial contributors to risk are environmental factors, including chemical and non-chemical stressors; yet, the paucity of mechanistic insights impedes prevention efforts. Here, we review the current literature and evaluate challenges to reducing liver cancer disparities. We also discuss the hypothesis that epigenetic mediators may provide biomarkers for early detection to support interventions that reduce disparities.}, journal={FRONTIERS IN ONCOLOGY}, author={Vidal, Adriana C. C. and Moylan, Cynthia A. A. and Wilder, Julius and Grant, Delores J. J. and Murphy, Susan K. K. and Hoyo, Cathrine}, year={2022}, month={Aug} }
 @article{king_sparling_lloyd_satusky_martinez_grenier_bergemann_maguire_hoyo_meyer_et al._2022, title={Sex-specific DNA methylation and associations with in utero tobacco smoke exposure at nuclear-encoded mitochondrial genes}, ISSN={["1559-2308"]}, DOI={10.1080/15592294.2022.2043591}, abstractNote={Sex-linked differences in mitochondrial ATP production, enzyme activities, and reactive oxygen species generation have been reported in multiple tissue and cell types. While the effects of reproductive hormones underlie many of these differences, regulation of sexually dimorphic mitochondrial function has not been fully characterized. We hypothesized that sex-specific DNA methylation contributes to sex-specific expression of nuclear genes that influence mitochondrial function. Herein, we analysed DNA methylation data specifically focused on nuclear-encoded mitochondrial genes in 191 males and 190 females. We found 596 differentially methylated sites (DMSs) (FDR p < 0.05), corresponding to 324 genes, with at least a 1% difference in methylation between sexes. To investigate the potential functional significance, we utilized gene expression microarray data. Of the 324 genes containing DMSs, 17 showed differences in gene expression by sex. Particularly striking was that ATP5G2, encoding subunit C of ATP synthase, contains seven DMSs and exhibits a sex difference in expression (p = 0.04). Finally, we also found that alterations in DNA methylation associated with in utero tobacco smoke exposure were sex-specific in these nuclear-encoded mitochondrial genes. Interestingly, the level of sex differences in DNA methylation at nuclear-encoded mitochondrial genes and the level of methylation changes associated with smoke exposure were less prominent than that of other genes. This suggests more conservative regulation of DNA methylation at these nuclear-encoded mitochondrial genes as compared to others. Overall, our findings suggest that sex-specific DNA methylation may help establish sex differences in expression and function and that sex-specific alterations in DNA methylation in response to exposures could contribute to sex-variable toxicological responses.}, journal={EPIGENETICS}, author={King, Dillon E. and Sparling, Anna Clare and Lloyd, Dillon and Satusky, Matthew Joseph and Martinez, Mackenzie and Grenier, Carole and Bergemann, Christina Michelle and Maguire, Rachel and Hoyo, Cathrine and Meyer, Joel Newman and et al.}, year={2022}, month={Mar} }
 @article{wheeler_boyle_barsell_maguire_zhang_oliver_jones_dahman_murphy_hoyo_et al._2022, title={Tobacco Retail Outlets, Neighborhood Deprivation and the Risk of Prenatal Smoke Exposure}, ISSN={["1469-994X"]}, DOI={10.1093/ntr/ntac164}, abstractNote={Abstract Introduction Smoking and smoke exposure among pregnant women remain persistent public health issues. Recent estimates suggest that approximately one out of four nonsmokers have measurable levels of cotinine, a marker indicating regular exposure to secondhand smoke. Epidemiological research has attempted to pinpoint individual-level and neighborhood-level factors for smoking during pregnancy. However, most of these studies have relied upon self-reported measures of smoking. Aims and Methods To more accurately assess smoke exposure resulting from both smoking and secondhand exposure in mothers during pregnancy, we used Bayesian regression models to estimate the association of cotinine levels with tobacco retail outlet (TRO) exposure and a neighborhood deprivation index (NDI) in six counties in North Carolina centered on Durham County. Results Results showed a significant positive association between TRO exposure (β = 0.008, 95% credible interval (CI) = [0.003, 0.013]) and log cotinine after adjusting for individual covariates (eg, age, race/ethnicity, education, marital status). TRO exposure was not significant after including the NDI, which was significantly associated with log cotinine (β = 0.143, 95% CI = [0.030, 0.267]). However, in a low cotinine stratum (indicating secondhand smoke exposure), TRO exposure was significantly associated with log cotinine (β = 0.005, 95% CI = [0.001, 0.009]), while in a high cotinine stratum (indicating active smoking), the NDI was significantly associated with log cotinine (β = 0.176, 95% CI = [0.005, 0.372]). Conclusions In summary, our findings add to the evidence that contextual factors are important for active smoking during pregnancy. Implications In this study, we found several significant associations that suggest a more nuanced understanding of the potential influence of environmental- and individual-level factors for levels of prenatal smoke exposure. Results suggested a significant positive association between TRO exposure and cotinine levels, after adjusting for the individual factors such as race, education, and marital status. Individually, NDI was similarly positively associated with cotinine levels as well. However, when combining TRO exposure alongside NDI in the same model, TROs were no longer significantly associated with overall cotinine levels.}, journal={NICOTINE & TOBACCO RESEARCH}, author={Wheeler, David C. and Boyle, Joseph and Barsell, D. Jeremy and Maguire, Rachel L. and Zhang, Junfeng and Oliver, Jason A. and Jones, Shawn and Dahman, Bassam and Murphy, Susan K. and Hoyo, Cathrine and et al.}, year={2022}, month={Jul} }
 @article{bosire_vidal_smith_jima_huang_skaar_valea_bentley_gradison_yarnall_et al._2021, title={Association between PEG3 DNA methylation and high-grade cervical intraepithelial neoplasia}, volume={16}, ISSN={["1750-9378"]}, DOI={10.1186/s13027-021-00382-3}, abstractNote={Epigenetic mechanisms are hypothesized to contribute substantially to the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, although empirical data are limited.Women (n = 419) were enrolled at colposcopic evaluation at Duke Medical Center in Durham, North Carolina. Human papillomavirus (HPV) was genotyped by HPV linear array and CIN grade was ascertained by biopsy pathologic review. DNA methylation was measured at differentially methylated regions (DMRs) regulating genomic imprinting of the IGF2/H19, IGF2AS, MESTIT1/MEST, MEG3, PLAGL1/HYMAI, KvDMR and PEG10, PEG3 imprinted domains, using Sequenom-EpiTYPER assays. Logistic regression models were used to evaluate the associations between HPV infection, DMR methylation and CIN risk overall and by race.Of the 419 participants, 20 had CIN3+, 52 had CIN2, and 347 had ≤ CIN1 (CIN1 and negative histology). The median participant age was 28.6 (IQR:11.6) and 40% were African American. Overall, we found no statistically significant association between altered methylation in selected DMRs and CIN2+ compared to ≤CIN1. Similarly, there was no significant association between DMR methylation and CIN3+ compared to ≤CIN2. Restricting the outcome to CIN2+ cases that were HR-HPV positive and p16 staining positive, we found a significant association with PEG3 DMR methylation (OR: 1.56 95% CI: 1.03-2.36).While the small number of high-grade CIN cases limit inferences, our findings suggest an association between altered DNA methylation at regulatory regions of PEG3 and high grade CIN in high-risk HPV positive cases.}, number={1}, journal={INFECTIOUS AGENTS AND CANCER}, author={Bosire, Claire and Vidal, Adriana C. and Smith, Jennifer S. and Jima, Dereje and Huang, Zhiqing and Skaar, David and Valea, Fidel and Bentley, Rex and Gradison, Margaret and Yarnall, Kimberly S. H. and et al.}, year={2021}, month={Jun} }
 @article{mueller_differding_ostbye_hoyo_benjamin-neelon_2021, title={Association of birth mode of delivery with infant faecal microbiota, potential pathobionts, and short chain fatty acids: a longitudinal study over the first year of life}, volume={128}, ISSN={["1471-0528"]}, DOI={10.1111/1471-0528.16633}, abstractNote={Caesarean section (CS) interrupts mother-to-newborn microbial transfer at birth. Beyond the neonatal period, the impact of CS on offspring gut microbiota and their short-chain fatty acids (SCFAs) remains unclear. Here, we examine birth delivery mode (CS versus vaginal delivery) with the infant gut microbiota and faecal SCFAs measured 3 and 12 months after birth.Longitudinal study.North Carolina.In 2013-15, we enrolled pregnant women and followed up their offspring for 12 months. We asked a subset of participants, enrolled over a 3-month period, to provide faecal samples at the 3- and 12-month follow-up visits.We sequenced the 16S rRNA V4 region with Illumina MiSeq and quantified SCFA concentrations using gas chromatography. We examined delivery mode with differential abundance of microbiota amplicon sequence variants (ASVs) using beta-binomial regression and faecal SCFAs using linear regression. We adjusted models for confounders.Of the 70 infants in our sample, 25 (36%) were delivered by CS. Compared with vaginal delivery, CS was associated with differential abundance of 14 infant bacterial ASVs at 3 months and 13 ASVs at 12 months (all FDR P < 0.05). Of note, CS infants had a higher abundance of the potential pathobionts Clostridium neonatale (P = 0.04) and Clostridium perfringens (P = 0.04) and a lower abundance of potentially beneficial Bifidobacterium and Bacteroides spp. (both P < 0.05) at 3 months. Other ASVs were differentially abundant at 12 months. Infants delivered by CS also had higher faecal butyrate concentration at 3 months (P < 0.005) but not at 12 months.Caesarean section was associated with increased butyrate excretion, decreased Bifidobacterium and Bacteroides spp., and more colonisation of the infant gut by pathobionts at 3 months of age. CS was also associated with altered gut microbiota composition, but not faecal SCFAs, at 12 months.Caesarean section delivery was associated with increased butyrate excretion, decreased Bifidobacterium, and increased colonisation of the infant gut by pathobionts at 3 months of age.}, number={8}, journal={BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY}, author={Mueller, N. T. and Differding, M. K. and ostbye, T. and Hoyo, C. and Benjamin-Neelon, S. E.}, year={2021}, month={Jul}, pages={1293–1303} }
 @article{monangi_xu_khanam_khan_deb_pervin_price_kennedy_al mahmud_fan_et al._2021, title={Association of maternal prenatal selenium concentration and preterm birth: a multicountry meta-analysis}, volume={6}, ISSN={["2059-7908"]}, DOI={10.1136/bmjgh-2021-005856}, abstractNote={Selenium (Se), an essential trace mineral, has been implicated in preterm birth (PTB). We aimed to determine the association of maternal Se concentrations during pregnancy with PTB risk and gestational duration in a large number of samples collected from diverse populations.Gestational duration data and maternal plasma or serum samples of 9946 singleton live births were obtained from 17 geographically diverse study cohorts. Maternal Se concentrations were determined by inductively coupled plasma mass spectrometry analysis. The associations between maternal Se with PTB and gestational duration were analysed using logistic and linear regressions. The results were then combined using fixed-effect and random-effect meta-analysis.In all study samples, the Se concentrations followed a normal distribution with a mean of 93.8 ng/mL (SD: 28.5 ng/mL) but varied substantially across different sites. The fixed-effect meta-analysis across the 17 cohorts showed that Se was significantly associated with PTB and gestational duration with effect size estimates of an OR=0.95 (95% CI: 0.9 to 1.00) for PTB and 0.66 days (95% CI: 0.38 to 0.94) longer gestation per 15 ng/mL increase in Se concentration. However, there was a substantial heterogeneity among study cohorts and the random-effect meta-analysis did not achieve statistical significance. The largest effect sizes were observed in UK (Liverpool) cohort, and most significant associations were observed in samples from Malawi.While our study observed statistically significant associations between maternal Se concentration and PTB at some sites, this did not generalise across the entire cohort. Whether population-specific factors explain the heterogeneity of our findings warrants further investigation. Further evidence is needed to understand the biologic pathways, clinical efficacy and safety, before changes to antenatal nutritional recommendations for Se supplementation are considered.}, number={9}, journal={BMJ GLOBAL HEALTH}, author={Monangi, Nagendra and Xu, Huan and Khanam, Rasheda and Khan, Waqasuddin and Deb, Saikat and Pervin, Jesmin and Price, Joan T. and Kennedy, Stephen H. and Al Mahmud, Abdullah and Fan, Yuemei and et al.}, year={2021}, month={Sep} }
 @article{maguire_house_lloyd_skinner_allen_raffi_skaar_park_mccullough_kollins_et al._2021, title={Associations between maternal obesity, gestational cytokine levels and child obesity in the NEST cohort}, volume={16}, ISSN={["2047-6302"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85098446153&partnerID=MN8TOARS}, DOI={10.1111/ijpo.12763}, abstractNote={Although maternal systemic inflammation is hypothesized to link maternal pre-pregnancy obesity to offspring metabolic dysfunction, patient empirical data are limited.In this study, we hypothesized that pre-pregnancy obesity alters systemic chemo/cytokines concentrations in pregnancy, and this alteration contributes to obesity in children.In a multi-ethnic cohort of 361 mother-child pairs, we measured prenatal concentrations of plasma TNF-α, IL-6, IL-8, IL-1β, IL-4, IFN-γ, IL-12 p70 subunit, and IL-17A using a multiplex ELISA and examined associations of pre-pregnancy obesity on maternal chemo/cytokine levels, and associations of these cytokine levels with offspring body mass index z score (BMI-z) at age 2-6 years using linear regression.After adjusting for maternal smoking, ethnicity, age, and education, pre-pregnancy obesity was associated with increased concentrations of TNF-α (P = .026) and IFN-γ (P = .06). While we found no evidence for associations between TNF-α concentrations and offspring BMI-z, increased IFN-γ concentrations were associated with decreased BMI-z (P = .0002), primarily in Whites (P = .0011). In addition, increased maternal IL-17A concentrations were associated with increased BMI-z in offspring (P = .0005) with stronger associations in African Americans (P = .0042) than Whites (P = .24).Data from this study are consistent with maternal obesity-related inflammation during pregnancy, increasing the risk of childhood obesity in an ethnic-specific manner.}, number={7}, journal={PEDIATRIC OBESITY}, author={Maguire, Rachel L. and House, John S. and Lloyd, Dillon T. and Skinner, Harlyn G. and Allen, Terrence K. and Raffi, Asifa Mohamed and Skaar, David A. and Park, Sarah S. and McCullough, Lauren E. and Kollins, Scott H. and et al.}, year={2021}, month={Jul} }
 @article{fuemmeler_dozmorov_do_zhang_grenier_huang_maguire_kollins_hoyo_murphy_2021, title={DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy: An Epigenome-Wide Association Study}, volume={129}, ISSN={["1552-9924"]}, DOI={10.1289/EHP8099}, abstractNote={Maternal smoking during pregnancy is related to altered DNA methylation in infant umbilical cord blood. The extent to which low levels of smoke exposure among nonsmoking pregnant women relates to offspring DNA methylation is unknown.This study sought to evaluate relationships between maternal prenatal plasma cotinine levels and DNA methylation in umbilical cord blood in newborns using the Infinium HumanMethylation 450K BeadChip.Participants from the Newborn Epigenetics Study cohort who reported not smoking during pregnancy had verified low levels of cotinine from maternal prenatal plasma (0 ng/mL to <4 ng/mL), and offspring epigenetic data from umbilical cord blood were included in this study (n=79). Multivariable linear regression models were fit to the data, controlling for cell proportions, age, race, education, and parity. Estimates represent changes in response to any 1-ng/mL unit increase in exposure.Multivariable linear regression models yielded 29,049 CpGs that were differentially methylated in relation to increases in cotinine at a 5% false discovery rate. Top CpGs were within or near genes involved in neuronal functioning (PRKG1, DLGAP2, BSG), carcinogenesis (FHIT, HSPC157) and inflammation (AGER). Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggest cotinine was related to methylation of gene pathways controlling neuronal signaling, metabolic regulation, cell signaling and regulation, and cancer. Further, enhancers associated with transcription start sites were enriched in altered CpGs. Using an independent sample from the same study population (n=115), bisulfite pyrosequencing was performed with infant cord blood DNA for two genes within our top 20 hits (AGER and PRKG1). Results from pyrosequencing replicated epigenome results for PRKG1 (cg17079497, estimate=-1.09, standard error (SE)=0.45, p=0.018) but not for AGER (cg09199225; estimate=-0.16, SE=0.21, p=0.44).Secondhand smoke exposure among nonsmoking women may alter DNA methylation in regions involved in development, carcinogenesis, and neuronal functioning. These novel findings suggest that even low levels of smoke exposure during pregnancy may be sufficient to alter DNA methylation in distinct sites of mixed umbilical cord blood leukocytes in pathways that are known to be altered in cord blood from pregnant active smokers. https://doi.org/10.1289/EHP8099.}, number={5}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Fuemmeler, Bernard F. and Dozmorov, Mikhail G. and Do, Elizabeth K. and Zhang, Junfeng and Grenier, Carole and Huang, Zhiqing and Maguire, Rachel L. and Kollins, Scott H. and Hoyo, Cathrine and Murphy, Susan K.}, year={2021}, month={May} }
 @article{lodge_hoyo_gutierrez_rappazzo_emch_martin_2021, title={Estimating exposure to neighborhood crime by race and ethnicity for public health research}, volume={21}, ISSN={["1471-2458"]}, DOI={10.1186/s12889-021-11057-4}, abstractNote={Police-reported crime data (hereafter "crime") is routinely used as a psychosocial stressor in public health research, yet few studies have jointly examined (a) differences in crime exposure based on participant race and ethnicity, (b) differences in measures of crime exposure, and (c) considerations for how exposure to police is captured in police-recorded crime data. We estimate neighborhood exposure to crime and discuss the implications of structural differences in exposure to crime and police based on race and ethnicity.Using GPS coordinates from 1188 participants in the Newborn Epigenetics Study, we estimated gestational exposure to crime provided by the Durham, North Carolina, Police Department within (a) 800 m and (b) the Census block group of residence. We controlled for non-overlapping spatial boundaries in crime, Census, residential, and police data to report crime spatial (crime per km2) and population (crime per 1000 people per km2) density.We demonstrate dramatic disparities in exposure to crime based on participant race and ethnicity and highlight variability in these disparities based on the type of crime and crime measurement method chosen.Public health researchers should give thoughtful consideration when using police-reported crime data to measure and model exposure to crime in the United States, as police-reported data encompasses joint exposure to police and crime in the neighborhood setting.}, number={1}, journal={BMC PUBLIC HEALTH}, author={Lodge, Evans K. and Hoyo, Cathrine and Gutierrez, Carmen M. and Rappazzo, Kristen M. and Emch, Michael E. and Martin, Chantel L.}, year={2021}, month={Jun} }
 @article{ksinan_sheng_do_schechter_zhang_maguire_hoyo_murphy_kollins_rubin_et al._2021, title={Identifying the Best Questions for Rapid Screening of Secondhand Smoke Exposure Among Children}, volume={23}, ISSN={["1469-994X"]}, DOI={10.1093/ntr/ntaa254}, abstractNote={Many children suffer from secondhand smoke exposure (SHSe), which leads to a variety of negative health consequences. However, there is no consensus on how clinicians can best query parents for possible SHSe among children. We employed a data-driven approach to create an efficient screening tool for clinicians to quickly and correctly identify children at risk for SHSe.Survey data from mothers and biospecimens from children were ascertained from the Neurodevelopment and Improving Children's Health following Environmental Tobacco Smoke Exposure (NICHES) study. Included were mothers and their children whose saliva were assayed for cotinine (n = 351 pairs, mean child age = 5.6 years). Elastic net regression predicting SHSe, as indicated from cotinine concentration, was conducted on available smoking-related questions and cross-validated with 2015-2016 National Health and Nutrition Examination Survey (NHANES) data to select the most predictive items of SHSe among children (n = 1670, mean child age = 8.4 years).Answering positively to at least one of the two final items ("During the past 30 days, did you smoke cigarettes at all?" and "Has anyone, including yourself, smoked tobacco in your home in the past 7 days?") showed area under the curve = .82, and good specificity (.88) and sensitivity (.74). These results were validated with similar items in the nationally representative NHANES sample, area under the curve = .82, specificity = .78, and sensitivity = .77.Our data-driven approach identified and validated two items that may be useful as a screening tool for a speedy and accurate assessment of SHSe among children.The current study used a rigorous data-driven approach to identify questions that could reliably predict SHSe among children. Using saliva cotinine concentration levels as a gold standard for determining SHSe, our analysis employing elastic net regression identified two questions that served as good classifier for distinguishing children who might be at risk for SHSe. The two items that we validated in the current study can be readily used by clinicians, such as pediatricians, as part of screening procedures to quickly identify whether children might be at risk for SHSe.}, number={7}, journal={NICOTINE & TOBACCO RESEARCH}, author={Ksinan, Albert J. and Sheng, Yaou and Do, Elizabeth K. and Schechter, Julia C. and Zhang, Junfeng and Maguire, Rachel L. and Hoyo, Cathrine and Murphy, Susan K. and Kollins, Scott H. and Rubin, Bruce and et al.}, year={2021}, month={Jul}, pages={1217–1223} }
 @article{freedland_muller_hoyo_turner_moorman_faria_carvalhal_reis_mauad_carvalho_et al._2021, title={Implications of Regionalizing Care in the Developing World: Impact of Distance to Referral Center on Compliance to Biopsy Recommendations in a Brazilian Prostate Cancer Screening Cohort}, volume={2021}, ISSN={["2090-312X"]}, DOI={10.1155/2021/6614838}, abstractNote={Given growing specialization in medical care, optimal care may require regionalization, which may create access barriers. We tested this within a large prostate cancer (PC) screening program in Brazil. In 2004–2007, Barretos Cancer Hospital prospectively screened men for PC throughout rural Brazil. Men with abnormal screen were referred for follow-up and possible biopsy. We tested the link between distance from screening site to Barretos Cancer Hospital and risk of noncompliance with showing up for biopsy, PC on biopsy and, among those with PC, PC grade using crude and multivariable logistic regression analysis. Among 10,467 men undergoing initial screen, median distance was 257 km (IQR: 135–718 km). On crude and multivariable analyses, farther distance was significantly linked with biopsy noncompliance (OR/100 km: 0.83, <math xmlns="http://www.w3.org/1998/Math/MathML" id="M1"> <mi>P</mi> <mo><</mo> <mn>0.001</mn> </math> ). Among men who lived within 150 km of Barretos Cancer Hospital, distance was unrelated to compliance (OR/100 km: 1.09, <math xmlns="http://www.w3.org/1998/Math/MathML" id="M2"> <mi>P</mi> <mo>=</mo> <mn>0.87</mn> </math> ). There was no association between distance and PC risk or PC grade (all <math xmlns="http://www.w3.org/1998/Math/MathML" id="M3"> <mi>P</mi> <mo>></mo> <mn>0.25</mn> </math> ). In Brazil, where distances to referral centers can be large, greater distance was related to reduced biopsy compliance in a PC screening cohort. Among men who lived within 150 km, distance was unrelated to compliance. Care regionalization may reduce access when distances are large.}, journal={PROSTATE CANCER}, author={Freedland, Alexis R. and Muller, Roberto L. and Hoyo, Cathrine and Turner, Elizabeth L. and Moorman, Patricia G. and Faria, Eliney F. and Carvalhal, Gustavo F. and Reis, Rodolfo B. and Mauad, Edmundo C. and Carvalho, Andre L. and et al.}, year={2021}, month={Jun} }
 @article{keyhan_burke_schrott_huang_grenier_price_raburn_corcoran_soubry_hoyo_et al._2021, title={Male obesity impacts DNA methylation reprogramming in sperm}, volume={13}, ISSN={["1868-7083"]}, DOI={10.1186/s13148-020-00997-0}, abstractNote={Male obesity has profound effects on morbidity and mortality, but relatively little is known about the impact of obesity on gametes and the potential for adverse effects of male obesity to be passed to the next generation. DNA methylation contributes to gene regulation and is erased and re-established during gametogenesis. Throughout post-pubertal spermatogenesis, there are continual needs to both maintain established methylation and complete DNA methylation programming, even during epididymal maturation. This dynamic epigenetic landscape may confer increased vulnerability to environmental influences, including the obesogenic environment, that could disrupt reprogramming fidelity. Here we conducted an exploratory analysis that showed that overweight/obesity (n = 20) is associated with differences in mature spermatozoa DNA methylation profiles relative to controls with normal BMI (n = 47).We identified 3264 CpG sites in human sperm that are significantly associated with BMI (p < 0.05) using Infinium HumanMethylation450 BeadChips. These CpG sites were significantly overrepresented among genes involved in transcriptional regulation and misregulation in cancer, nervous system development, and stem cell pluripotency. Analysis of individual sperm using bisulfite sequencing of cloned alleles revealed that the methylation differences are present in a subset of sperm rather than being randomly distributed across all sperm.Male obesity is associated with altered sperm DNA methylation profiles that appear to affect reprogramming fidelity in a subset of sperm, suggestive of an influence on the spermatogonia. Further work is required to determine the potential heritability of these DNA methylation alterations. If heritable, these changes have the potential to impede normal development.}, number={1}, journal={CLINICAL EPIGENETICS}, author={Keyhan, Sanaz and Burke, Emily and Schrott, Rose and Huang, Zhiqing and Grenier, Carole and Price, Thomas and Raburn, Doug and Corcoran, David L. and Soubry, Adelheid and Hoyo, Catherine and et al.}, year={2021}, month={Jan} }
 @article{soubry_murphy_vansant_he_price_hoyo_2021, title={Opposing Epigenetic Signatures in Human Sperm by Intake of Fast Food Versus Healthy Food}, volume={12}, ISSN={["1664-2392"]}, DOI={10.3389/fendo.2021.625204}, abstractNote={Animal experiments have demonstrated that diets high in fats create a harmful environment for developing sperm cells, contributing to impaired reproductive health and induced risk for chronic diseases in the next generation. Changes at the level of the epigenome have been suggested to underlie these observations. Human data are limited to verify this hypothesis. While we earlier demonstrated a link between male obesity and DNA methylation changes at imprinted genes in mature sperm cells and newborns, it is currently unknown if -or how- a paternal eating pattern (related to obesity) is related to indices for epigenetic inheritance. We here aim to examine a yet unexplored link between consumption of healthy (rich in vitamins and fibers) or unhealthy (“fast”) foods and methylation at imprint regulatory regions in DNA of sperm. We obtained semen and data from 67 men, as part of a North Carolina-based study: The Influence of the Environment on Gametic Epigenetic Reprogramming (TIEGER) study. Dietary data included intake of fruits/nuts, vegetables/soups, whole grain bread, meat, seafood/fish, and fatty or processed food items. Multiple regression models were used to explore the association between dietary habits and clinical sperm parameters as well as DNA methylation levels, quantified using bisulfite pyrosequencing at 12 differentially methylated regions (DMRs) of the following imprinted genes: GRB10 , IGF2 , H19 , MEG3 , NDN , NNAT , PEG1/MEST, PEG3 , PLAGL1 , SNRPN , and SGCE/PEG10 . After adjusting for age, obesity status and recruitment method, we found that Total Motile Count (TMC) was significantly higher if men consumed fruits/nuts (β=+6.9, SE=1.9, p=0.0005) and vegetables (β=+5.4, SE=1.9, p=0.006), whereas consumption of fries was associated with lower TMC (β=-20.2, SE=8.7, p=0.024). Semen volume was also higher if vegetables or fruits/nuts were frequently consumed (β=+0.06, SE=0.03, p=0.03). Similarly, our sperm epigenetic analyses showed opposing associations for healthy versus fast food items. Frequent consumption of fries was related to a higher chance of sperm being methylated at the MEG3-IG CpG4 site (OR=1.073, 95%CI: 1.035-1.112), and high consumption of vegetables was associated with a lower risk of DNA methylation at the NNAT CpG3 site (OR=0.941, 95%CI: 0.914-0.968). These results remained significant after adjusting for multiple testing. We conclude that dietary habits are linked to sperm epigenetic outcomes. If carried into the next generation paternal unhealthy dietary patterns may result in adverse metabolic conditions and increased risk for chronic diseases in offspring.}, journal={FRONTIERS IN ENDOCRINOLOGY}, author={Soubry, Adelheid and Murphy, Susan K. and Vansant, Greet and He, Yang and Price, Thomas M. and Hoyo, Cathrine}, year={2021}, month={Apr} }
 @article{fallavollita_do_schechter_kollins_zheng_qin_maguire_hoyo_murphy_fuemmeler_2021, title={Smoke-Free Home Rules and Association with Child Secondhand Smoke Exposure among Mother-Child Dyad Relationships}, volume={18}, ISSN={["1660-4601"]}, DOI={10.3390/ijerph18105256}, abstractNote={Smoke-free home rules restrict smoking in the home, but biomarkers of secondhand smoke exposure are needed to help understand the association between smoke-free homes and child secondhand smoke exposure. Participants (n = 346) were majority Black/African American mother–child dyads from a longitudinal study in North Carolina. Mothers completed questionnaires on household smoking behaviors and rules, and child saliva samples were assayed for secondhand smoke exposure. Regression models used smoke-free home rules to predict child risk for secondhand smoke exposure. Children in households with smoke-free home rules had less salivary cotinine and risk for secondhand smoke exposure. After controlling for smokers in the household, home smoking rules were not a significant predictor of secondhand smoke exposure. Compared to children in households with no smokers, children in households with at least one smoker but a non-smoking mother (OR 5.35, 95% CI: 2.22, 13.17) and households with at least one smoker including a smoking mother (OR 13.73, 95% CI: 6.06, 33.28) had greater risk for secondhand smoke exposure. Results suggest smoke-free home rules are not sufficient to fully protect children from secondhand smoke exposure, especially in homes with smokers. Future research should focus on how household members who smoke can facilitate the prevention of child secondhand smoke exposure.}, number={10}, journal={INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH}, author={Fallavollita, Westley L. and Do, Elizabeth K. and Schechter, Julia C. and Kollins, Scott H. and Zheng, Junfeng and Qin, Jian and Maguire, Rachel L. and Hoyo, Cathrine and Murphy, Susan K. and Fuemmeler, Bernard F.}, year={2021}, month={May} }
 @article{neumann_walton_alemany_cecil_gonzalez_jima_lahti_tuominen_barker_binder_et al._2020, title={Association between DNA methylation and ADHD symptoms from birth to school age: a prospective meta-analysis}, volume={10}, ISSN={["2158-3188"]}, DOI={10.1038/s41398-020-01058-z}, abstractNote={Abstract Attention-deficit and hyperactivity disorder (ADHD) is a common childhood disorder with a substantial genetic component. However, the extent to which epigenetic mechanisms play a role in the etiology of the disorder is unknown. We performed epigenome-wide association studies (EWAS) within the Pregnancy And Childhood Epigenetics (PACE) Consortium to identify DNA methylation sites associated with ADHD symptoms at two methylation assessment periods: birth and school age. We examined associations of both DNA methylation in cord blood with repeatedly assessed ADHD symptoms (age 4–15 years) in 2477 children from 5 cohorts and of DNA methylation at school age with concurrent ADHD symptoms (age 7–11 years) in 2374 children from 9 cohorts, with 3 cohorts participating at both timepoints. CpGs identified with nominal significance ( p < 0.05) in either of the EWAS were correlated between timepoints ( ρ = 0.30), suggesting overlap in associations; however, top signals were very different. At birth, we identified nine CpGs that predicted later ADHD symptoms ( p < 1 × 10 –7 ), including ERC2 and CREB5 . Peripheral blood DNA methylation at one of these CpGs (cg01271805 in the promoter region of ERC2 , which regulates neurotransmitter release) was previously associated with brain methylation. Another (cg25520701) lies within the gene body of CREB5 , which previously was associated with neurite outgrowth and an ADHD diagnosis. In contrast, at school age, no CpGs were associated with ADHD with p < 1 × 10 −7 . In conclusion, we found evidence in this study that DNA methylation at birth is associated with ADHD. Future studies are needed to confirm the utility of methylation variation as biomarker and its involvement in causal pathways.}, number={1}, journal={TRANSLATIONAL PSYCHIATRY}, author={Neumann, Alexander and Walton, Esther and Alemany, Silvia and Cecil, Charlotte and Gonzalez, Juan Ramon and Jima, Dereje D. and Lahti, Jari and Tuominen, Samuli T. and Barker, Edward D. and Binder, Elisabeth and et al.}, year={2020}, month={Nov} }
 @article{gonzalez-nahm_nihlani_s. house_l. maguire_g. skinner_hoyo_2020, title={Associations between Maternal Cadmium Exposure with Risk of Preterm Birth and Low after Birth Weight Effect of Mediterranean Diet Adherence on Affected Prenatal Outcomes}, volume={8}, ISSN={["2305-6304"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85094109102&partnerID=MN8TOARS}, DOI={10.3390/toxics8040090}, abstractNote={Prenatal cadmium exposure at non-occupational levels has been associated with poor birth outcomes. The intake of essential metals, such as iron and selenium, may mitigate cadmium exposure effects. However, at high levels, these metals can be toxic. The role of dietary patterns rich in these metals is less studied. We used a linear and logistic regression in a cohort of 185 mother–infant pairs to assess if a Mediterranean diet pattern during pregnancy modified the associations between prenatal cadmium exposure and (1) birth weight and (2) preterm birth. We found that increased cadmium exposure during pregnancy was associated with lower birth weight (β = −210.4; 95% CI: −332.0, −88.8; p = 0.008) and preterm birth (OR = 0.11; 95% CI: 0.01, 0.72; p = 0.04); however, these associations were comparable in offspring born to women reporting high adherence to a Mediterranean diet (β = −274.95; 95% CI: −701.17, 151.26; p = 0.20) and those with low adherence (β = −64.76; 95% CI: −359.90, 230.37; p = 0.66). While the small sample size limits inference, our findings suggest that adherence to a Mediterranean dietary pattern may not mitigate cadmium exposure effects. Given the multiple organs targeted by cadmium and its slow excretion rate, larger studies are required to clarify these findings.}, number={4}, journal={TOXICS}, publisher={MDPI AG}, author={Gonzalez-Nahm, Sarah and Nihlani, Kiran and S. House, John and L. Maguire, Rachel and G. Skinner, Harlyn and Hoyo, Cathrine}, year={2020}, month={Dec} }
 @article{fuemmeler_sheng_schechter_do_zucker_majors_maguire_murphy_hoyo_kollins_2020, title={Associations between attention deficit hyperactivity disorder symptoms and eating behaviors in early childhood}, volume={15}, ISSN={["2047-6302"]}, DOI={10.1111/ijpo.12631}, abstractNote={Attention-deficit/hyperactivity disorder (ADHD) symptoms have been linked with eating behaviors and obesity adolescence and young adulthood. Yet, little is known about whether these associations occur during early childhood and few studies have examined these associations prospectively.To assess magnitude and direction of associations between childhood ADHD symptoms and eating behaviors.Participants were from the Newborn Epigenetics Study (N = 470, M age = 4 years). Multivariable linear regression models were used to examine cross-sectional associations between ADHD symptoms and eating behaviors. Latent Change Score (LCS) modeling was performed to examine prospective association among a subset of children with available follow-up data. (N = 100, M age = 7 years).The cross-sectional results showed that attention problem (AP) and hyperactivity (HY) were positively associated with food responsiveness, emotional overeating, desire to drink, and slowness in eating. AP, but not HY, was inversely associated with enjoyment of food. Results of the LCS models revealed AP and HY were both positively associated with prospective changes in emotional overeating and satiety responsiveness. AP was further positively associated with prospective changes in food responsiveness. The reverse relationship predicting changes in ADHD symptoms from earlier assessments of eating behaviors was not significant.Results suggest a link between ADHD symptoms and obesity-related eating behaviors in early childhood, highlighting the need to address self-regulation and healthy eating behaviors in the prevention of childhood obesity.}, number={7}, journal={PEDIATRIC OBESITY}, author={Fuemmeler, Bernard F. and Sheng, Yaou and Schechter, Julia C. and Do, Elizabeth and Zucker, Nancy and Majors, Alesha and Maguire, Rachel and Murphy, Susan K. and Hoyo, Cathrine and Kollins, Scott H.}, year={2020}, month={Jul} }
 @article{vehmeijer_kuepers_sharp_salas_lent_jima_tindula_reese_qi_gruzieva_et al._2020, title={DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies}, volume={12}, ISSN={["1756-994X"]}, DOI={10.1186/s13073-020-00810-w}, abstractNote={DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits.We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment.DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10-7, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth Penrichment = 1; childhood Penrichment = 2.00 × 10-4; adolescence Penrichment = 2.10 × 10-7).There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.}, number={1}, journal={GENOME MEDICINE}, author={Vehmeijer, Florianne O. L. and Kuepers, Leanne K. and Sharp, Gemma C. and Salas, Lucas A. and Lent, Samantha and Jima, Dereje D. and Tindula, Gwen and Reese, Sarah and Qi, Cancan and Gruzieva, Olena and et al.}, year={2020}, month={Dec} }
 @article{benjamin-neelon_iversen_clancy_hoyo_bennett_kravitz_ostbye_2020, title={Early Child Care and Weight Status in a Cohort of Predominantly Black Infants in the Southeastern United States}, volume={16}, ISSN={["2153-2176"]}, DOI={10.1089/chi.2019.0127}, abstractNote={Background: Previous studies show inconsistent relations between child care and obesity, but few assessed longitudinal associations during infancy and even fewer included racially diverse children....}, number={2}, journal={CHILDHOOD OBESITY}, author={Benjamin-Neelon, Sara E. and Iversen, Edwin and Clancy, Shayna M. and Hoyo, Cathrine and Bennett, Gary G. and Kravitz, Richard M. and Ostbye, Truls}, year={2020}, month={Mar}, pages={122–128} }
 @article{schechter_do_zhang_hoyo_murphy_kollins_fuemmeler_2020, title={Effect of Prenatal Smoke Exposure on Birth Weight: The Moderating Role of Maternal Depressive Symptoms}, volume={22}, ISSN={["1469-994X"]}, DOI={10.1093/ntr/nty267}, abstractNote={Abstract Introduction Both prenatal smoke exposure and depression have been linked to lower birth weight, a risk factor for morbidity and mortality. Few studies have looked at the interaction between these risk factors and none have used a biomarker to objectively measure prenatal smoke exposure. The current study sought to examine independent and interactive effects of cotinine and depression on birth weight. The effect of race was also explored. Method Data were drawn from a prospective study of pregnant women (N = 568) in the southeastern United States. Maternal demographic, health information, depressive symptoms, and birth data were collected via self-report and medical record abstraction. Prenatal blood samples were assayed for cotinine. Results Controlling for covariates, multiple regression analyses indicated that both cotinine and depressive symptoms independently predicted lower birth weight and a significant interaction was also observed. Upon probing the interaction, a negative association between cotinine levels and birth weight was found in the context of higher depression but not lower depression scores. Similarly, logistic regression analyses revealed a significant interaction between cotinine and depression, such that cotinine predicted having a baby less than 2500 g among women who fell above the indicated cutoff score. African American women had the highest levels of cotinine and lowest weight babies; however, race was not a significant moderator. Conclusions Results suggest prenatal smoke exposure has a greater negative effect on birth weight for women endorsing co-occurring depressive symptoms. Findings can inform targeted interventions and assist medical providers with identifying women at increased risk for poor perinatal outcomes. Implications Despite the common occurrence of smoking during pregnancy and prenatal depression, the interaction between these risk factors on birth weight has rarely been examined. Further, the extant results have been mixed, likely due in part to difficulties in measurement. The current study was the first to use prenatal cotinine to assess bias-free, continuous levels of prenatal smoke exposure. Results indicate that prenatal cotinine was a significant predictor of birth weight only in the context of maternal depressive symptoms. These findings have important implications for mitigating negative perinatal outcomes for pregnant women and their children.}, number={1}, journal={NICOTINE & TOBACCO RESEARCH}, author={Schechter, Julia C. and Do, Elizabeth K. and Zhang, Junfeng and Hoyo, Cathrine and Murphy, Susan K. and Kollins, Scott H. and Fuemmeler, Bernard F.}, year={2020}, month={Jan}, pages={40–47} }
 @article{shafiee-kermani_carney_jima_utin_farrar_oputa_hines_kinyamu_trotter_archer_et al._2020, title={Expression of UDP Glucuronosyltransferases2B15and2B17is associated with methylation status in prostate cancer cells}, ISBN={1559-2308}, DOI={10.1080/15592294.2020.1795601}, abstractNote={Studies have suggested that abrogated expression of detoxification enzymes, UGT2B15 and UGT2B17, are associated with prostate tumour risk and progression. We investigated the role of EGF on the expression of these enzymes since it interacts with signalling pathways to also affect prostate tumour progression and is additionally associated with decreased DNA methylation. The expression of UGT2B15, UGT2B17, de novo methyltransferases, DNMT3A and DNMT3B was assessed in prostate cancer cells (LNCaP) treated with EGF, an EGFR inhibitor PD16893, and the methyltransferase inhibitor, 5-azacytidine, respectively. The results showed that EGF treatment decreased levels of expression of all four genes and that their expression was reversed by PD16893. Treatment with 5-azacytidine, markedly decreased expression of UGT2B15 and UGT2B17 over 85% as well as significantly decreased expression of DNMT3B, but not the expression of DNMT3A. DNMT3B siRNA treated LNCaP cells had decreased expression of UGT2B15 and UGT2B17, while DNMT3A siRNA treated cells had only moderately decreased UGT2B15 expression. Treatment with DNMT methyltransferase inhibitor, RG108, significantly decreased UGT2B17 expression. Additionally, methylation differences between prostate cancer samples and benign prostate samples from an Illumina 450K Methylation Array study were assessed. The results taken together suggest that hypomethylation of the UGT2B15 and UGT2B17 genes contributes to increased risk of prostate cancer and may provide a putative biomarker or epigenetic target for chemotherapeutics. Mechanistic studies are warranted to determine the role of the methylation marks in prostate cancer.}, journal={EPIGENETICS}, author={Shafiee-Kermani, Farideh and Carney, Skyla T. and Jima, Dereje and Utin, Utibe C. and Farrar, LaNeisha B. and Oputa, Melvin O. and Hines, Marcono R., Jr. and Kinyamu, H. Karimi and Trotter, Kevin W. and Archer, Trevor K. and et al.}, year={2020} }
 @article{oddo_hoyo_ostbye_benjamin-neelon_2020, title={Maternal Employment and Infant BMI z Score in a US Birth Cohort}, volume={28}, ISSN={["1930-739X"]}, DOI={10.1002/oby.23009}, abstractNote={The purpose of this study was to investigate the association between maternal employment and infant BMI z score.Longitudinal data from 520 mother-infant dyads participating in the Nurture Study, an observational cohort in the southeastern United States, were leveraged. Women were categorized as employed or nonemployed at 3, 6, 9, and 12 months, and measured anthropometrics were used to calculate infants' BMI z scores at the corresponding time points. BMI z score was defined using the World Health Organization standard. Household income was an effect modifier. Therefore, income-stratified (≤$40,000/y vs. >$40,000/y) linear regression models, with individual fixed effects, were used to examine associations between change in maternal employment status and BMI z scores among infants aged 3 to 12 months. Fixed effects controlled for time-invariant confounders (race/ethnicity, infant gender). This study also controlled for marital status and infant age.More women from higher-income (68.4%) versus lower-income households (52.6%) were employed. Among lower-income households, change from nonemployment to employment was associated with higher infant BMI z scores (β = 0.12; 95% CI: -0.01 to 0.25, P = 0.07). Among higher-income households, change in maternal employment status was associated with lower infant BMI z scores (β = -0.72; 95% CI: -1.17 to -0.27, P = 0.02).Maternal employment was related to infant adiposity. The direction of the association varied by household-level income.}, number={12}, journal={OBESITY}, author={Oddo, Vanessa M. and Hoyo, Cathrine and Ostbye, Truls and Benjamin-Neelon, Sara E.}, year={2020}, month={Dec}, pages={2389–2396} }
 @article{york_latendresse_jackson-cook_lapato_moyer_wolen_roberson-nay_do_murphy_hoyo_et al._2020, title={Replicated umbilical cord blood DNA methylation loci associated with gestational age at birth}, volume={15}, ISSN={["1559-2308"]}, DOI={10.1080/15592294.2020.1767277}, abstractNote={DNA methylation is highly sensitive to in utero perturbations and has an established role in both embryonic development and regulation of gene expression. The foetal genetic component has been previously shown to contribute significantly to the timing of birth, yet little is known about the identity and behaviour of individual genes. The aim of this study was to test the extent genome-wide DNA methylation levels in umbilical cord blood were associated with gestational age at birth (GA). Findings were validated in an independent sample and evidence for the regulation of gene expression was evaluated for cis gene relationships in specimens with multi-omic data. Genome-wide DNA methylation, measured by the Illumina Infinium Human Methylation 450 K BeadChip, was associated with GA for 2,372 CpG probes (5% FDR) in both the Pregnancy, Race, Environment, Genes (PREG) and Newborn Epigenetic Study (NEST) cohorts. Significant probes mapped to 1,640 characterized genes and an association with nearby gene expression measures obtained by the Affymetrix HG-133A microarray was found for 11 genes. Differentially methylated positions were enriched for actively transcribed and enhancer chromatin states, were predominately located outside of CpG islands, and mapped to genes enriched for inflammation and innate immunity ontologies. In both PREG and NEST, the first principal component derived from these probes explained approximately one-half (58.1% and 47.8%, respectively) of the variation in GA. Gene pathways identified are consistent with the hypothesis of pathogen detection and response by the immune system to elicit premature labour as a consequence of unscheduled inflammation.}, number={11}, journal={EPIGENETICS}, author={York, Timothy P. and Latendresse, Shawn J. and Jackson-Cook, Colleen and Lapato, Dana M. and Moyer, Sara and Wolen, Aaron R. and Roberson-Nay, Roxann and Do, Elizabeth K. and Murphy, Susan K. and Hoyo, Catherine and et al.}, year={2020}, month={Nov}, pages={1243–1258} }
 @article{huang_tzeng_maguire_hoyo_allen_2020, title={The association between neuraxial anesthesia and the development of childhood asthma - a secondary analysis of the newborn epigenetics study cohort}, volume={36}, ISSN={["1473-4877"]}, DOI={10.1080/03007995.2020.1747417}, abstractNote={Objectives Childhood asthma is a common chronic illness that has been associated with mode of delivery. However, the effect of cesarean delivery alone does not fully account for the increased prevalence of childhood asthma. We tested the hypothesis that neuraxial anesthesia used for labor analgesia and cesarean delivery alters the risk of developing childhood asthma.Methods Within the Newborn Epigenetics Study birth cohort, 196 mother and child pairs with entries in the electronic anesthesia records were included. From these records, data on maternal anesthesia type, duration of exposure, and drugs administered peripartum were abstracted and combined with questionnaire-derived prenatal risk factors and medical records and questionnaire-derived asthma diagnosis data in children. Logistic regression models were used to evaluate associations between type of anesthesia, duration of anesthesia, and the development of asthma in males and females.Results We found that longer duration of epidural anesthesia was associated with a lower risk of asthma in male children (OR = 0.80; 95% CI = 0.66–0.95) for each hour of epidural exposure. Additionally, a unit increase in the composite dose of local anesthetics and opioid analgesics administered via the spinal route was associated with a lower risk of asthma in both male (OR = 0.59, 95% CI = 0.36–0.96) and female children (OR 0.26, 95% CI 0.09–0.82).Conclusion Our data suggest that peripartum exposure to neuraxial anesthesia may reduce the risk of childhood asthma primarily in males. Larger human studies and model systems with longer follow-up are required to elucidate these findings.}, number={6}, journal={CURRENT MEDICAL RESEARCH AND OPINION}, author={Huang, Yueyang and Tzeng, Jung-Ying and Maguire, Rachel and Hoyo, Cathrine and Allen, Terrence}, year={2020}, month={Jun}, pages={1025–1032} }
 @article{differding_benjamin-neelon_hoyo_ostbye_mueller_2020, title={Timing of complementary feeding is associated with gut microbiota diversity and composition and short chain fatty acid concentrations over the first year of life}, volume={20}, ISSN={["1471-2180"]}, DOI={10.1186/s12866-020-01723-9}, abstractNote={Early introduction of complementary foods has been associated with various immune disorders, oxidative stress, and obesity in childhood. The gut microbiota and the short chain fatty acids (SCFAs) they produce are postulated to be on the causal pathway. The objective of this study was to determine if early complementary feeding (i.e. consumption of solids or non-water/formula liquids at or before 3 months) is prospectively associated with infant gut microbiota composition, diversity and SCFAs at 3 and 12 months of age in the Nurture birth cohort.Mother-infant dyads in the early complementary feeding group (n = 18) had similar baseline characteristics to those in the later feeding group (n = 49). We assessed differential abundance of microbial taxa (measured by 16S rRNA gene sequencing of the V4 region) by timing of complementary feeding using beta-binomial regression models (considering a two-sided FDR corrected p-value of < 0.05 as significant), and we fittted linear regression models to assess the association between early complementary feeding and SCFA concentrations (quantified using gas chromatography). After multivariable adjustment for breastfeeding, delivery method, birth weight, and gestational age, there were 13 differentially abundant microbial amplicon sequence variants (ASVs) by timing of introduction to complementary foods at 3 months and 20 ASVs at 12 months. Infants introduced to complementary foods early (vs. later) had higher concentrations of the SCFA butyric acid (mean difference = 0.65, 95% CI: 0.27, 1.04, p < 0.01) and total SCFAs (mean difference = 38.8, 95% CI: 7.83, 69.7) at 12 months. Bilophila wadsworthia and Lachnospiraceae Roseburia were associated with early (vs. later) complementary feeding and with higher butyric acid concentrations at 3 and 12 months, respectively.Our findings are consistent with the hypothesis that early (vs. later) introduction to complementary foods is associated with altered gut microbiota composition and butyric acid concentrations measured in stool until at least 1 year of age. Further research is needed to determine if these changes mediate future development of metabolic and immune conditions.}, number={1}, journal={BMC MICROBIOLOGY}, author={Differding, Moira K. and Benjamin-Neelon, Sara E. and Hoyo, Cathrine and ostbye, Truls and Mueller, Noel T.}, year={2020}, month={Mar} }
 @article{zhang_differding_benjamin-neelon_ostbye_hoyo_mueller_2019, title={Association of prenatal antibiotics with measures of infant adiposity and the gut microbiome}, volume={18}, ISSN={["1476-0711"]}, DOI={10.1186/s12941-019-0318-9}, abstractNote={Prenatal antibiotic exposure has been associated with an altered infant gut microbiome composition and higher risk of childhood obesity, but no studies have examined if prenatal antibiotics simultaneously alter the gut microbiome and adiposity in infants.In this prospective study (Nurture: recruitment 2013-2015 in North Carolina, United States), we examined in 454 infants the association of prenatal antibiotic exposure (by any prenatal antibiotic exposure; by trimester of pregnancy; by number of courses; by type of antibiotics) with infant age- and sex-specific weight-for-length z score (WFL-z) and skinfold thicknesses (subscapular, triceps, abdominal) at 12 months of age. In a subsample, we also examined whether prenatal antibiotic exposure was associated with alterations in the infant gut microbiome at ages 3 and 12 months.Compared to infants not exposed to prenatal antibiotics, infants who were exposed to any prenatal antibiotics had 0.21 (95% confidence interval [CI] 0.02, 0.41) higher WFL-z at 12 months, and 0.28 (95% CI 0.02, 0.55) higher WFL-z if they were exposed to antibiotics in the second trimester, after adjustment for potential confounders, birth weight, and gestational age. We also observed a dose-dependent association (P-value for trend = 0.006) with infants exposed to ≥ 3 courses having 0.41 (95% CI 0.13, 0.68) higher WFL-z at 12 months. After further adjustment for delivery method, only second-trimester antibiotic exposure remained associated with higher infant WFL-z (0.27, 95% CI 0.003, 0.54) and subscapular skinfold thickness (0.49 mm, 95% CI 0.11, 0.88) at 12 months. Infants exposed to second-trimester antibiotics versus not had differential abundance of 13 bacterial amplicon sequence variants (ASVs) at age 3 months and 17 ASVs at 12 months (false discovery rate adjusted P-value < 0.05).Prenatal antibiotic exposure in the second trimester was associated with an altered infant gut microbiome composition at 3 and 12 months and with higher infant WFL-z and subscapular skinfold thickness at 12 months.}, journal={ANNALS OF CLINICAL MICROBIOLOGY AND ANTIMICROBIALS}, author={Zhang, Mingyu and Differding, Moira K. and Benjamin-Neelon, Sara E. and Ostbye, Truls and Hoyo, Cathrine and Mueller, Noel T.}, year={2019}, month={Jun} }
 @article{howe_zhou_wang_pittman_thompson_campbell_bastain_grubbs_salam_hoyo_et al._2019, title={Associations between Maternal Tobacco Smoke Exposure and the Cord Blood CD4(+) DNA Methylome}, volume={127}, ISSN={["1552-9924"]}, DOI={10.1289/EHP3398}, abstractNote={Background: Maternal tobacco smoke exposure has been associated with altered DNA methylation. However, previous studies largely used methylation arrays, which cover a small fraction of CpGs, and focused on whole cord blood. Objectives: The current study examined the impact of in utero exposure to maternal tobacco smoke on the cord blood CD4+ DNA methylome. Methods: The methylomes of 20 Hispanic white newborns (n=10 exposed to any maternal tobacco smoke in pregnancy; n=10 unexposed) from the Maternal and Child Health Study (MACHS) were profiled by whole-genome bisulfite sequencing (median coverage: 6.5×). Statistical analyses were conducted using the Regression Analysis of Differential Methylation (RADMeth) program because it performs well on low-coverage data (minimizes false positives and negatives). Results: We found that 10,381 CpGs were differentially methylated by tobacco smoke exposure [neighbor-adjusted p-values that are additionally corrected for multiple testing based on the Benjamini-Hochberg method for controlling the false discovery rate (FDR) (pFDR)<0.05]. From these CpGs, RADMeth identified 557 differentially methylated regions (DMRs) that were overrepresented (p<0.05) in important regulatory regions, including enhancers. Of nine DMRs that could be queried in a reduced representation bisulfite sequencing (RRBS) study of adult CD4+ cells (n=9 smokers; n=10 nonsmokers), four replicated (p<0.05). Additionally, a CpG in the promoter of SLC7A8 (percent methylation difference: −9.4% comparing exposed to unexposed) replicated (p<0.05) in an EPIC (Illumina) array study of cord blood CD4+ cells (n=14 exposed to sustained maternal tobacco smoke; n=16 unexposed) and in a study of adult CD4+ cells across two platforms (EPIC: n=9 smokers; n=11 nonsmokers; 450K: n=59 smokers; n=72 nonsmokers). Conclusions: Maternal tobacco smoke exposure in pregnancy is associated with cord blood CD4+ DNA methylation in key regulatory regions, including enhancers. While we used a method that performs well on low-coverage data, we cannot exclude the possibility that some results may be false positives. However, we identified a differentially methylated CpG in amino acid transporter SLC7A8 that is highly reproducible, which may be sensitive to cigarette smoke in both cord blood and adult CD4+ cells. https://doi.org/10.1289/EHP3398}, number={4}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Howe, Caitlin G. and Zhou, Meng and Wang, Xuting and Pittman, Gary S. and Thompson, Isabel J. and Campbell, Michelle R. and Bastain, Theresa M. and Grubbs, Brendan H. and Salam, Muhammad T. and Hoyo, Cathrine and et al.}, year={2019}, month={Apr} }
 @article{do_zucker_huang_schechter_kollins_maguire_murphy_hoyo_fuemmeler_2019, title={Associations between imprinted gene differentially methylated regions, appetitive traits and body mass index in children}, volume={14}, ISSN={["2047-6302"]}, DOI={10.1111/ijpo.12454}, abstractNote={Background Knowledge regarding genetic influences on eating behaviours is expanding; yet less is known regarding contributions of epigenetic variation to appetitive traits and body mass index (BMI) in children. Objective The purpose of this study was to explore relationships between methylation at differentially methylated regions (DMRs) of imprinted genes (insulin-like growth factor 2/H19 and Delta-like, Drosophila, homolog 1/maternally expressed gene 3) using DNA extracted from umbilical cord blood leucocytes, two genetically influenced appetitive traits (food responsiveness and satiety responsiveness) and BMI. Methods Data were obtained from participants (N = 317; mean age = 3.6 years; SD = 1.8 years) from the Newborn Epigenetic STudy. Conditional process models were implemented to investigate the associations between DMRs of imprinted genes and BMI, and test whether this association was mediated by appetitive traits and birthweight and moderated by sex. Results Appetitive traits and birthweight did not mediate the relationship between methylation at DMRs. Increased insulin-like growth factor 2 DMR methylation was associated with higher satiety responsiveness. Higher satiety responsiveness was associated with lower BMI. Associations between methylation at DMRs, appetitive traits and BMI differed by sex. Conclusions This is one of the first studies to demonstrate associations between epigenetic variation established prior to birth with appetitive traits and BMI in children, providing support for the need to uncover genetic and epigenetic mechanisms for appetitive traits predisposing some individuals to obesity.}, number={2}, journal={PEDIATRIC OBESITY}, author={Do, E. K. and Zucker, N. L. and Huang, Z. Y. and Schechter, J. C. and Kollins, S. H. and Maguire, R. L. and Murphy, S. K. and Hoyo, C. and Fuemmeler, B. F.}, year={2019}, month={Feb} }
 @article{gonzalez-nahm_hoyo_ostbye_neelon_allen_benjamin-neelon_2019, title={Associations of maternal diet with infant adiposity at birth, 6 months and 12 months}, volume={9}, ISSN={["2044-6055"]}, DOI={10.1136/bmjopen-2019-030186}, abstractNote={Objectives To assess associations between maternal prenatal diet quality and infant adiposity. Design The design was a prospective birth cohort. Setting We used data from the Nurture study, a cohort of women and their infants residing in the southeastern USA. Participants and exposure assessment Between 2013 and 2015, we enrolled 860 women between 20 and 36 weeks’ gestation. After reconsenting at delivery and excluding women with implausible calorie intakes, we measured dietary intake using the Block food frequency questionnaire, and assessed diet quality using a modified Alternate Healthy Eating Index 2010 (AHEI-2010), which assessed intake of 10 food categories, including fruits, vegetables, whole grains, nuts/legumes, fats, meats, beverages and sodium (excluding alcohol). Outcomes We assessed birth weight for gestational age z-score, small and large for gestational age, low birth weight and macrosomia. Outcomes at 6 and 12 months were weight-for-length z-score, sum of subscapular and triceps skinfold thickness (SS+TR) and subscapular-to-triceps skinfold ratio (SS:TR). Results Among mothers, 70.2% were black and 20.9% were white; less than half (45.2%) reported having a high school diploma or less. Among infants, 8.7% were low birth weight and 8.6% were small for gestational age. Unadjusted estimates showed that a higher AHEI-2010 score, was associated with a higher birth weight for gestational z-score (β=0.01; 95% CI 0.002 to 0.02; p=0.02) and a greater likelihood of macrosomia (OR=1.04; 95% CI 1.004 to 1.09; p=0.03). After adjustment, maternal diet quality was not associated with infant adiposity at birth, 6 or 12 months. Conclusions Although poor maternal diet quality during pregnancy was not associated with infant adiposity in our study, maternal diet during pregnancy may still be an important and modifiable factor of public health importance.}, number={9}, journal={BMJ OPEN}, author={Gonzalez-Nahm, Sarah and Hoyo, Cathrine and Ostbye, Truls and Neelon, Brian and Allen, Carter and Benjamin-Neelon, Sara E.}, year={2019}, month={Sep} }
 @article{sikdar_joehanes_joubert_xu_vives-usano_rezwan_felix_ward_guan_richmond_et al._2019, title={Comparison of smoking-related DNA methylation between newborns from prenatal exposure and adults from personal smoking}, volume={11}, ISSN={["1750-192X"]}, DOI={10.2217/epi-2019-0066}, abstractNote={Aim: Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for in utero exposure in newborns is unknown. Materials & methods: We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and personal smoking (16 cohorts, 15907 participants, 2433 current smokers). Results & conclusion: Comparing meta-analyses, we identified numerous signatures specific to newborns along with many shared between newborns and adults. Unique smoking-associated genes in newborns were enriched in xenobiotic metabolism pathways. Our findings may provide insights into specific health impacts of prenatal exposure on offspring.}, number={13}, journal={EPIGENOMICS}, author={Sikdar, Sinjini and Joehanes, Roby and Joubert, Bonnie R. and Xu, Cheng-Jian and Vives-Usano, Marta and Rezwan, Faisal I. and Felix, Janine F. and Ward, James M. and Guan, Weihua and Richmond, Rebecca C. and et al.}, year={2019}, month={Oct}, pages={1487–1500} }
 @article{xie_leung_chen_long_hoyo_ho_2019, title={Differential methylation values in differential methylation analysis}, volume={35}, ISSN={["1460-2059"]}, DOI={10.1093/bioinformatics/bty778}, abstractNote={Both β-value and M-value have been used as metrics to measure methylation levels. The M-value is more statistically valid for the differential analysis of methylation levels. However, the β-value is much more biologically interpretable and needs to be reported when M-value method is used for conducting differential methylation analysis. There is an urgent need to know how to interpret the degree of differential methylation from the M-value. In M-value linear regression model, differential methylation M-value ΔM can be easily obtained from the coefficient estimate, but it is not straightforward to get the differential methylation β-value, Δβ since it cannot be obtained from the coefficient alone.To fill the gap, we have built a bridge to connect the statistically sound M-value linear regression model and the biologically interpretable Δβ. In this article, three methods were proposed to calculate differential methylation values, Δβ from M-value linear regression model and compared with the Δβ directly obtained from β-value linear regression model. We showed that under the condition that M-value linear regression model is correct, the method M-model-coef is the best among the four methods. M-model-M-mean method works very well too. If the coefficients α0, α2,…αp are not given (as 'MethLAB' package), the M-model-M-mean method should be used. The Δβ directly obtained from β-value linear regression model can give very biased results, especially when M-values are not in (-2, 2) or β-values are not in (0.2, 0.8).The dataset for example is available at the National Center for Biotechnology Information Gene Expression Omnibus repository, GSE104778.Supplementary data are available at Bioinformatics online.}, number={7}, journal={BIOINFORMATICS}, author={Xie, Changchun and Leung, Yuet-Kin and Chen, Aimin and Long, Ding-Xin and Hoyo, Catherine and Ho, Shuk-Mei}, year={2019}, month={Apr}, pages={1094–1097} }
 @article{mueller_zhang_hoyo_ostbye_benjamin-neelon_2019, title={Does cesarean delivery impact infant weight gain and adiposity over the first year of life?}, volume={43}, ISSN={["1476-5497"]}, DOI={10.1038/s41366-018-0239-2}, abstractNote={Potentially driven by the lack of mother-to-infant transmission of microbiota at birth, cesarean delivery has been associated with higher risk of offspring obesity. Yet, no studies have examined when delivery-mode differences in adiposity begin to emerge. In this study, we examine differences in infant weight and adiposity trajectories from birth to 12 months by delivery mode.From 2013 to 2015, we recruited pregnant women into the Nurture Study and followed up their 666 infants. We ascertained maternal delivery method and infant birth weight from medical records. We measured weight, length, and skinfold thicknesses (subscapular, triceps, abdominal) when infants were 3, 6, 9, and 12 months of age. The main outcome, infant weight-for-length z score, was derived based on the WHO Child Growth Standards. We used linear regression models to assess the difference at each time point and used linear mixed models to examine the growth rate for infant weight and adiposity trajectories. We controlled for maternal age, race, marital status, education level, household income, smoking status, maternal pre-pregnancy body mass index, and infant birth weight.Of the 563 infants in our final sample, 179 (31.8%) were cesarean delivered. From birth to 12 months, the rate of increase in weight-for-length z score was 0.02/month (p = 0.03) greater for cesarean-delivered than vaginally-delivered infants. As a result of more rapid growth, cesarean-delivered infants had higher weight-for-length z score (0.26, 95% CI: 0.05, 0.47) and sum of subscapular and triceps (SS + TR) skinfold thickness (0.95 mm, 95% CI: 0.30, 1.60)-an indicator for overall adiposity-at 12 months, compared to vaginally-delivered infants.Compared to vaginal delivery, cesarean delivery was associated with greater offspring rate of weight gain over the first year and differences in adiposity that appear as early as 3 months of age. Monitoring cesarean-delivered infants closely for excess weight gain may help guide primordial prevention of obesity later in life.}, number={8}, journal={INTERNATIONAL JOURNAL OF OBESITY}, author={Mueller, Noel T. and Zhang, Mingyu and Hoyo, Cathrine and Ostbye, Truls and Benjamin-Neelon, Sara E.}, year={2019}, month={Aug}, pages={1549–1555} }
 @article{chawla_fuemmeler_benjamin-neelon_hoyo_murphy_daniels_2019, title={Early prenatal vitamin D concentrations and social-emotional development in infants}, volume={32}, ISSN={["1476-4954"]}, DOI={10.1080/14767058.2017.1408065}, abstractNote={Background: Many pregnant women in the United States have suboptimal vitamin D, but the impact on infant development is unclear. Moreover, no pregnancy-specific vitamin D recommendations have been widely accepted.Aims: Given the ubiquitous expression of vitamin D receptors in the brain, we investigated the association between early prenatal plasma 25-hydroxyvitamin D (25(OH)D) concentrations and children’s social and emotional development in the Newborn Epigenetic Study, a prospective study of pregnancies from 2009 to 2011 in Durham, North Carolina.Methods: We measured 25(OH)D concentrations in first or second trimester plasma samples and categorized 25(OH)D concentrations into quartiles. Covariates were derived from maternal questionnaires. Mothers completed the Infant Toddler Social-Emotional Development Assessment when children were 12–24 months of age. We used multivariable linear regression to evaluate associations between 25(OH)D and specific behavior scores, adjusted for season of blood draw, maternal age, education, parity, smoking, marital status, prepregnancy BMI, and infant gender. We investigated effect-measure modification by race/ethnicity.Results: Of the 218 mother–infant pairs with complete data, Black mothers had much lower 25(OH)D concentrations as compared to White and Hispanic mothers. After adjustment, lower prenatal 25(OH)D was associated with slightly higher (less favorable) Internalizing scores among White children, but lower (more favorable) Internalizing scores among Black and Hispanic children. Lower prenatal 25(OH)D also appears to be associated with higher (less favorable) dysregulation scores, though only among White and Hispanic children.Conclusions: Though imprecise, preliminary results warrant further investigation regarding a role for prenatal vitamin D on children’s early social and emotional development.}, number={9}, journal={JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE}, author={Chawla, Devika and Fuemmeler, Bernard and Benjamin-Neelon, Sara E. and Hoyo, Cathrine and Murphy, Susan and Daniels, Julie L.}, year={2019}, month={May}, pages={1441–1448} }
 @article{sorrow_maguire_murphy_belcher_hoyo_2019, title={Elevated metabolites of acetaminophen in cord blood of children with obesity}, volume={14}, ISSN={["2047-6302"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85053785805&partnerID=MN8TOARS}, DOI={10.1111/ijpo.12465}, abstractNote={Background High-throughput metabolomics has been used cross-sectionally to evaluate differential metabolic profiles associated with human obesity. Objectives This study longitudinally assessed the cord blood metabolome to explore if metabolic signatures of obesity at age 3–5 are apparent at birth. Methods In a nested case–control design, metabolomics analysis was performed on umbilical cord blood of 25 children who developed obesity by age 3–5 years, compared with 25 sex-matched non-obese children enrolled as part of an ongoing birth cohort. Logistic regression models were used to identify significant metabolites, adjusting for maternal pre-pregnancy obesity. Results Children who had obesity by age 3–5 years had elevated levels of medium and long chain fatty acids including stearate, oleate and palmitate at birth. Children with obesity were also more likely to have elevated levels of acetaminophen metabolites at birth, specifically: 3-(N-acetyl-L-cystein-S-yl) acetaminophen, 2-hydroxyacetaminophen sulfate, 2-methoxyacetaminophen glucuronide and p-acetamidophenyl glucuronide. Conclusion Although the observed increases in lipids are consistent with previous metabolomic studies of obesity, this study is the first to report associations between acetaminophen metabolites and obesity in children; however, we lack mechanistic insights for this link. Larger human studies with longer follow-up and laboratory-controlled animal experiments are needed to clarify associations.}, number={1}, journal={PEDIATRIC OBESITY}, author={Sorrow, P. and Maguire, R. and Murphy, S. K. and Belcher, S. M. and Hoyo, C.}, year={2019}, month={Jan} }
 @article{reese_xu_dekker_lee_sikdar_ruiz-arenas_merid_rezwan_page_ullemar_et al._2019, title={Epigenome-wide meta-analysis of DNA methylation and childhood asthma}, volume={143}, ISSN={["1097-6825"]}, DOI={10.1016/j.jaci.2018.11.043}, abstractNote={Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis.We sought to identify differential DNA methylation in newborns and children related to childhood asthma.Within the Pregnancy And Childhood Epigenetics consortium, we performed epigenome-wide meta-analyses of school-age asthma in relation to CpG methylation (Illumina450K) in blood measured either in newborns, in prospective analyses, or cross-sectionally in school-aged children. We also identified differentially methylated regions.In newborns (8 cohorts, 668 cases), 9 CpGs (and 35 regions) were differentially methylated (epigenome-wide significance, false discovery rate < 0.05) in relation to asthma development. In a cross-sectional meta-analysis of asthma and methylation in children (9 cohorts, 631 cases), we identified 179 CpGs (false discovery rate < 0.05) and 36 differentially methylated regions. In replication studies of methylation in other tissues, most of the 179 CpGs discovered in blood replicated, despite smaller sample sizes, in studies of nasal respiratory epithelium or eosinophils. Pathway analyses highlighted enrichment for asthma-relevant immune processes and overlap in pathways enriched both in newborns and children. Gene expression correlated with methylation at most loci. Functional annotation supports a regulatory effect on gene expression at many asthma-associated CpGs. Several implicated genes are targets for approved or experimental drugs, including IL5RA and KCNH2.Novel loci differentially methylated in newborns represent potential biomarkers of risk of asthma by school age. Cross-sectional associations in children can reflect both risk for and effects of disease. Asthma-related differential methylation in blood in children was substantially replicated in eosinophils and respiratory epithelium.}, number={6}, journal={JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY}, author={Reese, Sarah E. and Xu, Cheng-Jian and Dekker, Herman T. and Lee, Mi Kyeong and Sikdar, Sinjini and Ruiz-Arenas, Carlos and Merid, Simon K. and Rezwan, Faisal I and Page, Christian M. and Ullemar, Vilhelmina and et al.}, year={2019}, month={Jun}, pages={2062–2074} }
 @article{grant_manichaikul_alberg_bandera_barnholtz-sloan_bondy_cote_funkhouser_moorman_peres_et al._2019, title={Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women}, volume={8}, ISSN={["2045-7634"]}, DOI={10.1002/cam4.1996}, abstractNote={An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom-designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high-grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 1.2 × 10−6, BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6-3.4, P = 1.6 × 10−5, BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 2.3 × 10−5, BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC.}, number={5}, journal={CANCER MEDICINE}, author={Grant, Delores J. and Manichaikul, Ani and Alberg, Anthony J. and Bandera, Elisa V and Barnholtz-Sloan, Jill and Bondy, Melissa and Cote, Michele L. and Funkhouser, Ellen and Moorman, Patricia G. and Peres, Lauren C. and et al.}, year={2019}, month={May}, pages={2503–2513} }
 @article{michael_oyekunle_howard_de hoedt_hoyo_grant_freedland_2019, title={Interplay between exercise and BMI; results from an equal access, racially diverse biopsy study}, volume={30}, ISSN={["1573-7225"]}, DOI={10.1007/s10552-018-1104-2}, number={1}, journal={CANCER CAUSES & CONTROL}, author={Michael, Jamie and Oyekunle, Taofik and Howard, Lauren and De Hoedt, Amanda and Hoyo, Catherine and Grant, Delores and Freedland, Stephen}, year={2019}, month={Jan}, pages={13–20} }
 @article{martin_jima_sharp_mccullough_park_gowdy_skaar_cowley_maguire_fuemmeler_et al._2019, title={Maternal pre-pregnancy obesity, offspring cord blood DNA methylation, and offspring cardiometabolic health in early childhood: an epigenome-wide association study}, volume={14}, ISSN={["1559-2308"]}, url={https://doi.org/10.1080/15592294.2019.1581594}, DOI={10.1080/15592294.2019.1581594}, abstractNote={Pre-pregnancy obesity is an established risk factor for adverse sex-specific cardiometabolic health in offspring. Epigenetic alterations, such as in DNA methylation (DNAm), are a hypothesized link; however, sex-specific epigenomic targets remain unclear. Leveraging data from the Newborn Epigenetics Study (NEST) cohort, linear regression models were used to identify CpG sites in cord blood leukocytes associated with pre-pregnancy obesity in 187 mother-female and 173 mother-male offsprings. DNAm in cord blood was measured using the Illumina HumanMethylation450k BeadChip. Replication analysis was conducted among the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Associations between pre-pregnancy obesity-associated CpG sites and offspring BMI z-score (BMIz) and blood pressure (BP) percentiles at 4–5-years of age were also examined. Maternal pre-pregnacy obesity was associated with 876 CpGs in female and 293 CpGs in male offspring (false discovery rate <5%). Among female offspring, 57 CpG sites, including the top 18, mapped to the TAPBP gene (range of effect estimates: −0.83% decrease to 4.02% increase in methylation). CpG methylation differences in the TAPBP gene were also observed among males (range of effect estimates: −0.30% decrease to 2.59% increase in methylation). While technically validated, none of the TAPBP CpG sites were replicated in ALSPAC. In NEST, methylation differences at CpG sites of the TAPBP gene were associated with BMI z-score (cg23922433 and cg17621507) and systolic BP percentile (cg06230948) in female and systolic (cg06230948) and diastolic (cg03780271) BP percentile in male offspring. Together, these findings suggest sex-specific effects, which, if causal, may explain observed sex-specific effects of maternal obesity.}, number={4}, journal={EPIGENETICS}, author={Martin, Chantel L. and Jima, Dereje and Sharp, Gemma C. and McCullough, Lauren E. and Park, Sarah S. and Gowdy, Kymberly M. and Skaar, David and Cowley, Michael and Maguire, Rachel L. and Fuemmeler, Bernard and et al.}, year={2019}, month={Apr}, pages={325–340} }
 @article{kupers_monnereau_sharp_yousefi_salas_ghantous_page_reese_wilcox_czamara_et al._2019, title={Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight}, volume={10}, ISSN={["2041-1723"]}, DOI={10.1038/s41467-019-09671-3}, abstractNote={Abstract Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (P Bonferroni < 1.06 x 10 −7 ). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10 −74 ) and BMI in pregnancy (3/914, p = 1.13x10 −3 ), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.}, journal={NATURE COMMUNICATIONS}, author={Kupers, Leanne K. and Monnereau, Claire and Sharp, Gemma C. and Yousefi, Paul and Salas, Lucas A. and Ghantous, Akram and Page, Christian M. and Reese, Sarah E. and Wilcox, Allen J. and Czamara, Darina and et al.}, year={2019}, month={Apr} }
 @article{josey_mccullough_hoyo_williams-devane_2019, title={Overall gestational weight gain mediates the relationship between maternal and child obesity}, volume={19}, ISSN={["1471-2458"]}, DOI={10.1186/s12889-019-7349-1}, abstractNote={Approximately 17% of children in the U.S. are obese. Children that are overweight or obese are also more likely to be obese as adults and suffer from various chronic diseases and premature death. Maternal obesity can affect the weight status of her offspring through intrauterine mechanisms like excessive gestational weight gain (GWG). Current literature shows a positive association between maternal weight status and GWG on child obesity, yet the direct and indirect effects have not been decomposed or quantified. The purpose of this study was to estimate the effect of maternal obesity on child obesity, mediated by GWG, which is a modifiable risk factor.The study participants were a birth cohort of offspring from women who received prenatal care in the Duke/Durham Regional health care system in Durham, NC between 2005 and 2009. Anthropomorphic data was collected via electronic medical records (EMRs) during each voluntary visit to a health care facility. The exposure of interest was maternal obesity, measured by pre-pregnancy body mass index, the mediator was GWG, dichotomized into excessive and not excessive based on maternal prenatal BMI, and the outcome was child obesity at age 4, measured as BMI z-scores from the last recorded height and weight. A counterfactual theory-based product method analysis estimated the mediated effects of GWG, adjusted for maternal race, socioeconomic status, and smoking status.Of the 766 children, 25% were overweight or obese, and among all mothers, 25 and 31% were overweight and obese, respectively. Maternal BMI was associated with an overall increase of 0.04 in offspring z-score. The proportion of the effect of maternal obesity on child age 4 obesity mediated by GWG was 8.1%.GWG, in part, mediated the relationship between maternal BMI and childhood adiposity. Even when the mediator is fixed, children are at an increased risk of a higher BMI if the mother is obese. These findings highlight an important public health education opportunity to stress the impact of a pre-pregnancy weight and excessive GWG on the risk of child obesity for all mothers.}, number={1}, journal={BMC PUBLIC HEALTH}, author={Josey, Michele J. and McCullough, Lauren E. and Hoyo, Cathrine and Williams-DeVane, ClarLynda}, year={2019}, month={Aug} }
 @article{fuemmeler_zucker_sheng_sanchez_maguire_murphy_kollins_hoyo_2019, title={Pre-Pregnancy Weight and Symptoms of Attention Deficit Hyperactivity Disorder and Executive Functioning Behaviors in Preschool Children}, volume={16}, ISSN={["1660-4601"]}, DOI={10.3390/ijerph16040667}, abstractNote={This study examines pre-pregnancy Body Mass Index (BMI) and gestational weight gain (GWG) in relation to early childhood Attention Deficit Hyperactivity Disorder (ADHD) symptoms and related executive self-regulation behaviors. The analyses sample (n = 331) included a subsample of participants from a birth cohort recruited from prenatal clinics and hospital facilities from April 2005 to June 2011 in Durham, North Carolina. Pre-pregnancy BMI was calculated from weight at the last menstrual period and height was extracted from medical records. Gestational weight gain was calculated from pre-pregnancy weight and weight measured at the time of delivery. ADHD symptoms and executive self-regulation behaviors were assessed by maternal report (mean age = 3 years). Multivariable regression methods with inverse probability weighting (IPW) were used to evaluate associations accounting for sample selection bias and confounding. Pre-pregnancy BMI at levels ≥35 was positively associated with higher ADHD symptoms and worse executive self-regulation behaviors (inhibitory control and attention). Compared to adequate GWG, less than adequate GWG was related to more ADHD hyperactive-impulsive symptoms, whereas greater than adequate GWG was related to more problematic behaviors related to working memory and planning. The findings support a link between maternal weight and child neurodevelopment. Continued research that help identify biological mechanisms are needed.}, number={4}, journal={INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH}, author={Fuemmeler, Bernard F. and Zucker, Nancy and Sheng, Yaou and Sanchez, Carmen E. and Maguire, Rachel and Murphy, Susan K. and Kollins, Scott H. and Hoyo, Cathrine}, year={2019}, month={Feb} }
 @article{skinner_lumey_fleming_sapienza_hoyo_aronica_thompson_nichol_2019, title={RW-2018-Research Workshop: The Effect of Nutrition on Epigenetic Status, Growth, and Health}, volume={43}, ISSN={["1941-2444"]}, DOI={10.1002/jpen.1536}, abstractNote={The goal of the 2018 American Society for Parenteral and Enteral Nutrition (ASPEN) Research Workshop was to explore the influence of nutrition and dietary exposure to xenobiotics on the epigenome during critical periods in development and how these exposures influence both disease incidence and severity transgenerationally. A growing compendium of research indicates that the incidence and severity of common and costly human diseases may be influenced by dietary exposures and deficiencies that modify the epigenome. The greatest periods of vulnerability to these exposures are the periconception period and early childhood. Xenobiotics in the food chain, protein malnutrition, and methyl donor deficiencies could have a profound bearing on the risk of developing heart disease, diabetes, obesity, hypertension, and mental illness over multiple generations. The financial impact and the life burden of these diseases are enormous. These and other aspects of nutrition, epigenetics, and health are explored in this research workshop.}, number={5}, journal={JOURNAL OF PARENTERAL AND ENTERAL NUTRITION}, author={Skinner, Michael and Lumey, L. H. and Fleming, Tom P. and Sapienza, Carmen and Hoyo, Cathrine and Aronica, Lucia and Thompson, Jeff and Nichol, Peter F.}, year={2019}, month={Jul}, pages={627–637} }
 @article{chawla_daniels_benjamin-neelon_fuemmeler_hoyo_buckley_2019, title={Racial and ethnic differences in predictors of vitamin D among pregnant women in south-eastern USA}, volume={8}, ISSN={["2048-6790"]}, DOI={10.1017/jns.2019.4}, abstractNote={Abstract Insufficient vitamin D during pregnancy increases risk of adverse outcomes, with known differences by race/ethnicity. We sought to determine whether predictors of vitamin D insufficiency vary by race/ethnicity in an ethnically diverse pregnancy cohort. Plasma 25-hydroxyvitamin D concentrations and patient characteristics were measured at first prenatal visit to prenatal clinics in south-eastern USA between 2009 and 2011 ( n 504). Prevalence ratios (PR) and 95 % CI were estimated using multivariable regression to quantify predictors of vitamin D insufficiency, overall and by race/ethnicity. In race/ethnicity-stratified models, season was most associated with vitamin D insufficiency among non-Hispanic white women; PR for winter v. summer were 3·58 (95 % CI 1·64, 7·81) for non-Hispanic white, 1·52 (95 % CI 1·18, 1·95) for Hispanic and 1·14 (95 % CI 0·99, 1·30) for non-Hispanic black women. Although women with darker skin tones are most vulnerable to prenatal vitamin D insufficiency, season may be more strongly associated with insufficiency among women with lighter skin tones.}, journal={JOURNAL OF NUTRITIONAL SCIENCE}, author={Chawla, Devika and Daniels, Julie L. and Benjamin-Neelon, Sara E. and Fuemmeler, Bernard F. and Hoyo, Cathrine and Buckley, Jessie P.}, year={2019}, month={Feb} }
 @article{bergens_pittman_thompson_campbell_wang_hoyo_bell_2019, title={Smoking-associated AHRR demethylation in cord blood DNA: impact of CD235a+nucleated red blood cells}, volume={11}, ISSN={["1868-7083"]}, DOI={10.1186/s13148-019-0686-1}, abstractNote={Numerous studies have demonstrated that DNA methylation levels in the aryl hydrocarbon receptor repressor (AHRR) gene measured in cord blood are significantly associated with prenatal tobacco smoke exposure and can be used as a fetal exposure biomarker. The mechanism driving this demethylation has not been determined and it is unclear if all cord blood cell types are impacted. Nucleated red blood cells (nRBCs/CD235a+ cells) are developmentally immature RBCs that display genome-wide hypomethylation and are observed at increased frequency in the cord blood of smoking mothers. We tested if AHRR methylation levels in CD235a+ nRBCs or nRBC counts influenced AHRR methylation in whole cord blood. Cord blood was collected from smoking (n = 34) and nonsmoking (n = 19) mothers and DNA was prepared from whole cord blood, isolated CD235a+ nRBCs, and CD14+ monocytes. AHRR methylation in cord blood DNA was measured using Illumina 850K arrays (cg05575921, chr5:373378). Pyrosequencing was used to compare methylation levels among cord blood, CD235a+, and CD14+ cells. We measured nRBC percentages using conventional complete blood counts and estimated percent nRBCs by a deconvolution model. Methylation levels in AHRR were significantly lower in nRBCs relative to whole cord blood and CD14+ monocytes. While AHRR methylation levels in the cell types were significantly correlated across all subjects, methylation values at the chr5:373378 CpG averaged 14.6% lower in nRBCs (range 0.4 to 24.8%; p = 3.8E−13) relative to CD14+, with nonsmokers showing a significantly greater hypomethylation (− 4.1%, p = 1.8E−02). Methylation level at the AHRR chr5:373378 CpG was strongly associated with self-reported smoking in both CD14+ monocytes (t test p = 5.7E−09) and nRBCs (p = 4.8E−08), as well as cotinine levels (regression p = 1.1E−07 and p = 3.6E−04, respectively). For subjects with whole blood 850K data, robust linear regression models adjusting for estimated cell type composition, either including nRBCs counts or estimates, modestly increased the association between smoking and cg05575921 methylation. Prenatal smoke exposure was highly significantly associated with AHRR methylation in cord blood, CD14+ monocytes, and CD235a+ nRBCs. AHRR methylation levels in nRBCs and nRBC counts had minimal effect on cord blood methylation measurements. However, regression models using estimated nRBCs or actual nRBC counts outperformed those lacking these covariates.}, journal={CLINICAL EPIGENETICS}, author={Bergens, Matthew A. and Pittman, Gary S. and Thompson, Isabel J. B. and Campbell, Michelle R. and Wang, Xuting and Hoyo, Cathrine and Bell, Douglas A.}, year={2019}, month={Jun} }
 @article{xue_maguire_liu_kollins_murphy_hoyo_fuemmeler_2019, title={Snacking frequency and dietary intake in toddlers and preschool children}, volume={142}, ISSN={["1095-8304"]}, DOI={10.1016/j.appet.2019.104369}, abstractNote={Understanding the relationship between snacking and dietary intake in early life years is one key but understudied area. In this study, we examined snacking patterns in toddlers and preschool children and the associations between snacking frequency and daily energy intake. We analyzed data from children aged 12-72 months (N = 1186) in the Newborn Epigenetic STudy (NEST). We used Bonferroni multiple comparison methods to examine the differences in snacking patterns across subgroups. Linear and quantile regression models were fit to investigate the association between dietary intake and snacking frequency. Our estimates suggest that Non-Hispanic blacks had the highest total daily energy intake from snacks (334 kcal/day) compared to non-Hispanic whites (270 kcal/day) and Hispanics (274 kcal/day) in 12-to-24-month-olds. In 2-to-6-year-olds, mean energy intake from snacks was 296 kcal/day without a significant racial/ethnic difference. Carbohydrate, fat and protein from snacks contributed about 17%, 9% and 4% respectively of the total energy intake in 12-to-24-month-olds while they contributed about 15%, 7% and 2% respectively of the total energy intake in the other age group. Snacking frequency was positively and significantly associated with total daily energy intake in both 12-to-24-month-olds and 2-to-6-year-olds as indicated by regression coefficient estimates of snacking frequency (β = 31.3 kcal/day with P = 0.027 and β = 175.4 kcal/day with P < 0.0001, respectively, indicating a higher snacking frequency was associated with a greater total daily energy intake). In conclusion, snacking frequency was positively associated with daily energy intake. Carbohydrates and fats from snacks are significant energy contributors. Age differentiation was apparent regarding the relationship between snacking frequency and dietary intake. Differentiated interventions that are age-specific and focus on the dietary quality of snacks instead of quantity are needed.}, journal={APPETITE}, author={Xue, Hong and Maguire, Rachel L. and Liu, Jin and Kollins, Scott H. and Murphy, Susan K. and Hoyo, Cathrine and Fuemmeler, Bernard F.}, year={2019}, month={Nov} }
 @article{dozmorov_bilbo_kollins_zucker_do_schechter_zhang_murphy_hoyo_fuemmeler_2018, title={Associations between maternal cytokine levels during gestation and measures of child cognitive abilities and executive functioning}, volume={70}, ISSN={["1090-2139"]}, DOI={10.1016/j.bbi.2018.03.029}, abstractNote={Preclinical studies demonstrate that environmentally-induced alterations in inflammatory cytokines generated by the maternal and fetal immune system can significantly impact fetal brain development. Yet, the relationship between maternal cytokines during gestation and later cognitive ability and executive function remains understudied. Children (n = 246) were born of mothers enrolled in the Newborn Epigenetic Study – a prospective pre-birth cohort in the Southeastern US. We characterized seven cytokines [IL-1β, IL-4,IL-6, IL-12p70, IL-17A, tumor necrosis factor-α (TNFα), and interferon-γ (IFNγ)] and one chemokine (IL-8) from maternal plasma collected during pregnancy. We assessed children’s cognitive abilities and executive functioning at a mean age of 4.5 (SD = 1.1) years. Children’s DAS-II and NIH toolbox scores were regressed on cytokines and the chemokine, controlling for maternal age, race, education, body mass index, IQ, parity, smoking status, delivery type, gestational weeks, and child birth weight and sex. Higher IL-12p70 (βIL-12p70 = 4.26, p = 0.023) and IL-17A (βIL-17A = 3.70, p = 0.042) levels were related to higher DAS-II GCA score, whereas higher IL-1β (βIL-1B = −6.07, p = 0.003) was related to lower GCA score. Higher IL-12p70 was related to higher performance on NIH toolbox measures of executive functions related to inhibitory control and attention (βIL-12p70 = 5.20, p = 0.046) and cognitive flexibility (βIL-12p70 = 5.10, p = 0.047). Results suggest that dysregulation in gestational immune activity are associated with child cognitive ability and executive functioning.}, journal={BRAIN BEHAVIOR AND IMMUNITY}, author={Dozmorov, Mikhail G. and Bilbo, Staci D. and Kollins, Scott H. and Zucker, Nancy and Do, Elizabeth K. and Schechter, Julia C. and Zhang, Junfeng and Murphy, Susan K. and Hoyo, Cathrine and Fuemmeler, Bernard F.}, year={2018}, month={May}, pages={390–397} }
 @article{green_hoyo_mattingly_luo_tzeng_murphy_buchwalter_planchart_2018, title={Cadmium exposure increases the risk of juvenile obesity: a human and zebrafish comparative study}, volume={42}, ISSN={0307-0565 1476-5497}, url={http://dx.doi.org/10.1038/S41366-018-0036-Y}, DOI={10.1038/S41366-018-0036-Y}, abstractNote={Human obesity is a complex metabolic disorder disproportionately affecting people of lower socioeconomic strata, and ethnic minorities, especially African Americans and Hispanics. Although genetic predisposition and a positive energy balance are implicated in obesity, these factors alone do not account for the excess prevalence of obesity in lower socioeconomic populations. Therefore, environmental factors, including exposure to pesticides, heavy metals, and other contaminants, are agents widely suspected to have obesogenic activity, and they also are spatially correlated with lower socioeconomic status. Our study investigates the causal relationship between exposure to the heavy metal, cadmium (Cd), and obesity in a cohort of children and in a zebrafish model of adipogenesis.An extensive collection of first trimester maternal blood samples obtained as part of the Newborn Epigenetics Study (NEST) was analyzed for the presence of Cd, and these results were cross analyzed with the weight-gain trajectory of the children through age 5 years. Next, the role of Cd as a potential obesogen was analyzed in an in vivo zebrafish model.Our analysis indicates that the presence of Cd in maternal blood during pregnancy is associated with increased risk of juvenile obesity in the offspring, independent of other variables, including lead (Pb) and smoking status. Our results are recapitulated in a zebrafish model, in which exposure to Cd at levels approximating those observed in the NEST study is associated with increased adiposity.Our findings identify Cd as a potential human obesogen. Moreover, these observations are recapitulated in a zebrafish model, suggesting that the underlying mechanisms may be evolutionarily conserved, and that zebrafish may be a valuable model for uncovering pathways leading to Cd-mediated obesity in human populations.}, number={7}, journal={International Journal of Obesity}, publisher={Springer Science and Business Media LLC}, author={Green, Adrian J. and Hoyo, Cathrine and Mattingly, Carolyn J. and Luo, Yiwen and Tzeng, Jung-Ying and Murphy, Susan K. and Buchwalter, David B. and Planchart, Antonio}, year={2018}, month={Feb}, pages={1285–1295} }
 @article{felix_joubert_baccarelli_sharp_almqvist_annesi-maesano_arshad_baiz_bakermans-kranenburg_bakulski_et al._2018, title={Cohort profile: Pregnancy and childhood epigenetics (PACE) consortium}, volume={47}, number={1}, journal={International Journal of Epidemiology}, author={Felix, J. F. and Joubert, B. R. and Baccarelli, A. A. and Sharp, G. C. and Almqvist, C. and Annesi-Maesano, I. and Arshad, H. and Baiz, N. and Bakermans-Kranenburg, M. J. and Bakulski, K. M. and et al.}, year={2018}, pages={22-} }
 @article{gomih_smith_north_hudgens_brewster_huang_skaar_valea_bentley_vidal_et al._2018, title={DNA methylation of imprinted gene control regions in the regression of low-grade cervical lesions}, volume={143}, ISSN={["1097-0215"]}, DOI={10.1002/ijc.31350}, abstractNote={The role of host epigenetic mechanisms in the natural history of low-grade cervical intraepithelial neoplasia (CIN1) is not well characterized. We explored differential methylation of imprinted gene regulatory regions as predictors of the risk of CIN1 regression. A total of 164 patients with CIN1 were recruited from 10 Duke University clinics for the CIN Cohort Study. Participants had colposcopies at enrollment and up to five follow-up visits over 3 years. DNA was extracted from exfoliated cervical cells for methylation quantitation at CpG (cytosine-phosphate-guanine) sites and human papillomavirus (HPV) genotyping. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression to quantify the effect of methylation on CIN1 regression over two consecutive visits, compared to non-regression (persistent CIN1; progression to CIN2+; or CIN1 regression at a single time-point), adjusting for age, race, high-risk HPV (hrHPV), parity, oral contraceptive and smoking status. Median participant age was 26.6 years (range: 21.0-64.4 years), 39% were African-American, and 11% were current smokers. Most participants were hrHPV-positive at enrollment (80.5%). Over one-third of cases regressed (n = 53, 35.1%). Median time-to-regression was 12.6 months (range: 4.5-24.0 months). Probability of CIN1 regression was negatively correlated with methylation at IGF2AS CpG 5 (HR = 0.41; 95% CI = 0.23-0.77) and PEG10 DMR (HR = 0.80; 95% CI = 0.65-0.98). Altered methylation of imprinted IGF2AS and PEG10 DMRs may play a role in the natural history of CIN1. If confirmed in larger studies, further research on imprinted gene DMR methylation is warranted to determine its efficacy as a biomarker for cervical cancer screening.}, number={3}, journal={INTERNATIONAL JOURNAL OF CANCER}, author={Gomih, Ayodele and Smith, Jennifer S. and North, Kari E. and Hudgens, Michael G. and Brewster, Wendy R. and Huang, Zhiqing and Skaar, David and Valea, Fidel and Bentley, Rex C. and Vidal, Adriana C. and et al.}, year={2018}, month={Aug}, pages={552–560} }
 @article{gonzalez-nahm_mendez_benjamin-neelon_murphy_hogan_rowley_hoyo_2018, title={DNA methylation of imprinted genes at birth is associated with child weight status at birth, 1 year, and 3 years}, volume={10}, journal={Clinical Epigenetics}, author={Gonzalez-Nahm, S. and Mendez, M. A. and Benjamin-Neelon, S. E. and Murphy, S. K. and Hogan, V. K. and Rowley, D. L. and Hoyo, C.}, year={2018} }
 @article{hoyo_skaar_park_sorrow_2018, title={EPIGENOMICS AND HUMAN OBESITY}, volume={6}, ISBN={["978-0-12-812215-0"]}, DOI={10.1016/B978-0-12-812215-0.00014-5}, abstractNote={Abstract Obesity has become one of the most urgent public health problems globally with the steepest increases in prevalence reported among socioeconomically disadvantaged and ethnic minorities. Obesity is associated with sizable reductions in life expectancy and quality of life. Although evidence from model systems supports that epigenetic dysregulation may cause obesity, the affected pathways are still unclear. This chapter summarizes human data on CpG methylation, the most studied epigenetic mechanism in humans, in the context of causal inference, in adults and children. Recent technological advances in the measurement of CpG methylation have led to the identification of multiple obesity-related sequence regions. Still limited are data on the temporal stability of regions identified thus far, and the extent to which obesity-related sequence regions remain significant in ethnic minorities. We conclude with a call for sex- and ethnic-specific data, together with data demonstrating that obesity-associated DNA methylation marks identified precede obesity.}, journal={EPIGENETICS IN HUMAN DISEASE, 2ND EDITION}, author={Hoyo, Cathrine and Skaar, David A. and Park, Sarah S. and Sorrow, Patricia}, year={2018}, pages={409–426} }
 @article{cowley_skaar_jima_maguire_hudson_park_sorrow_hoyo_2018, title={Effects of cadmium exposure on DNA methylation at imprinting control regions and genome-wide in mothers and newborn children}, volume={126}, number={3}, journal={Environmental Health Perspectives}, author={Cowley, M. and Skaar, D. A. and Jima, D. D. and Maguire, R. L. and Hudson, K. M. and Park, S. S. and Sorrow, P. and Hoyo, C.}, year={2018} }
 @article{planchart_green_hoyo_mattingly_2018, title={Heavy Metal Exposure and Metabolic Syndrome: Evidence from Human and Model System Studies}, volume={5}, ISSN={2196-5412}, url={http://dx.doi.org/10.1007/S40572-018-0182-3}, DOI={10.1007/S40572-018-0182-3}, abstractNote={Metabolic syndrome (MS) describes the co-occurrence of conditions that increase one's risk for heart disease and other disorders such as diabetes and stroke. The worldwide increase in the prevalence of MS cannot be fully explained by lifestyle factors such as sedentary behavior and caloric intake alone. Environmental exposures, such as heavy metals, have been implicated, but results are conflicting and possible mechanisms remain unclear. To assess recent progress in determining a possible role between heavy metal exposure and MS, we reviewed epidemiological and model system data for cadmium (Cd), lead (Pb), and mercury (Hg) from the last decade.Data from 36 epidemiological studies involving 17 unique countries/regions and 13 studies leveraging model systems are included in this review. Epidemiological and model system studies support a possible association between heavy metal exposure and MS or comorbid conditions; however, results remain conflicting. Epidemiological studies were predominantly cross-sectional and collectively, they highlight a global interest in this question and reveal evidence of differential susceptibility by sex and age to heavy metal exposures. In vivo studies in rats and mice and in vitro cell-based assays provide insights into potential mechanisms of action relevant to MS including altered regulation of lipid and glucose homeostasis, adipogenesis, and oxidative stress. Heavy metal exposure may contribute to MS or comorbid conditions; however, available data are conflicting. Causal inference remains challenging as epidemiological data are largely cross-sectional; and variation in study design, including samples used for heavy metal measurements, age of subjects at which MS outcomes are measured; the scope and treatment of confounding factors; and the population demographics vary widely. Prospective studies, standardization or increased consistency across study designs and reporting, and consideration of molecular mechanisms informed by model system studies are needed to better assess potential causal links between heavy metal exposure and MS.}, number={1}, journal={Current Environmental Health Reports}, publisher={Springer Science and Business Media LLC}, author={Planchart, Antonio and Green, Adrian and Hoyo, Cathrine and Mattingly, Carolyn J.}, year={2018}, month={Feb}, pages={110–124} }
 @article{schechter_fuemmeler_hoyo_murphy_zhang_kollins_2018, title={Impact of smoking ban on passive smoke exposure in pregnant non-smokers in the Southeastern United States}, volume={15}, number={1}, journal={International Journal of Environmental Research and Public Health}, author={Schechter, J. C. and Fuemmeler, B. F. and Hoyo, C. and Murphy, S. K. and Zhang, J. F. and Kollins, S. H.}, year={2018} }
 @article{neelon_white_vidal_schildkraut_murtha_murphy_kullman_hoyo_2018, title={Maternal vitamin D, DNA methylation at imprint regulatory regions and offspring weight at birth, 1 year and 3 years}, volume={42}, ISSN={["1476-5497"]}, DOI={10.1038/ijo.2017.160}, abstractNote={Vitamin D deficiency during pregnancy is associated with poor birth outcomes in some studies, but few have examined weight beyond birth. In addition, little is known about how vitamin D influences DNA methylation of regulatory regions known to be involved in growth, as possible mediators to weight status in offspring. We conducted linear regressions to assess maternal plasma 25-hydroxyvitamin D (25(OH)D) by quartile and birth weight for gestational age z-score, 1-year weight-for-length z-score and 3-year body mass index (BMI) z-score among 476 mother/infant dyads from a prospective cohort. We assessed maternal 25(OH)D and infant DNA methylation at nine differentially methylated regions (DMRs) of genomically imprinted genes with known functions in fetal growth, including H19, IGF2, MEG3, MEG3-IG, MEST, NNAT, PEG3, PLAGL1 and SGCE/PEG10. Mean (standard deviation, s.d.) maternal 25(OH)D was 41.1 (14.2) nmol l−m at a mean (s.d.) of 13.2 (5.5) weeks gestation. After adjustment for potential confounders, the first (Q1) and second (Q2) quartiles of 25(OH)D, compared to the fourth (Q4), were associated with lower birth weight for gestational age z-scores (−0.43 units; CI: −0.79, −0.07; P=0.02 for Q1 and −0.56 units; CI: −0.89, −0.23; P=0.001 for Q2). Q1 compared to Q4 was associated with higher 1-year weight-for-length z-scores (0.78 units; 0.08, 1.54; P=0.04) and higher 3-year BMI z-scores (0.83 units; 0.11, 0.93; P=0.02). We did not observe associations between maternal 25(OH)D and methylation for any of the nine DMRs after correcting for multiple testing. Reduced maternal 25(OH)D was associated with lower birth weight for gestational age z-scores but higher 1-year weight-for-length and 3-year BMI z-scores in offspring. However, 25(OH)D does not appear to be operating through the regulatory sequences of the genomically imprinted genes we examined.}, number={4}, journal={INTERNATIONAL JOURNAL OF OBESITY}, author={Neelon, S. E. Benjamin and White, A. J. and Vidal, A. C. and Schildkraut, J. M. and Murtha, A. P. and Murphy, S. K. and Kullman, S. W. and Hoyo, C.}, year={2018}, month={Apr}, pages={587–593} }
 @article{house_mendez_maguire_gonzalez-nahm_huang_daniels_murphy_fuemmeler_wright_hoyo_2018, title={Periconceptional maternal mediterranean diet is associated with favorable offspring behaviors and altered CpG methylation of imprinted genes}, volume={6}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85053720031&partnerID=MN8TOARS}, DOI={10.3389/fcell.2018.00107}, abstractNote={Background: Maternal diet during pregnancy has been shown to influence the child neuro-developmental outcomes. Studies examining effects of dietary patterns on offspring behavior are sparse. Objective: Determine if maternal adherence to a Mediterranean diet is associated with child behavioral outcomes assessed early in life, and to evaluate the role of differentially methylated regions (DMRs) regulating genomically imprinted genes in these associations. Methods: Among 325 mother/infant pairs, we used regression models to evaluate the association between tertiles of maternal periconceptional Mediterranean diet adherence (MDA) scores derived from a Food Frequency Questionnaire, and social and emotional scores derived from the Infant Toddler Social and Emotional Assessment (ITSEA) questionnaire in the second year of life. Methylation of nine genomically imprinted genes was measured to determine if MDA was associated with CpG methylation. Results: Child depression was significantly associated with maternal MDA (Bonferroni-corrected p = 0.048). While controlling for false-discovery, compared to offspring of women with the lowest MDA tertile, those with MDA scores in middle and high MDA tertiles had decreased odds for atypical behaviors (OR (95%CI) = 0.40 (0.20, 0.78) for middle and 0.40 (0.17, 0.92) for highest tertile)), for maladaptive behaviors (0.37 (0.18, 0.72) for middle tertile and 0.42 (0.18, 0.95) for highest tertile) and for an index of autism spectrum disorder behaviors (0.46 (0.23, 0.90) for middle and 0.35 (0.15, 0.80) for highest tertile). Offspring of women with the highest MDA tertile were less likely to exhibit depressive (OR=0.28 (0.12, 0.64)) and anxiety (0.42 (0.18, 0.97)) behaviors and increased odds of social relatedness (2.31 (1.04, 5.19)) behaviors when compared to low MDA mothers. Some associations varied by sex. Perinatal MDA score was associated with methylation differences for imprinted control regions of PEG10/SGCE (females: Beta (95%CI) = 1.66 (0.52, 2.80) - Bonferroni-corrected p = 0.048; males: -0.56 (-1.13, -0.00)), as well as both MEG3 and IGF2 in males (0.97 (0.00, 1.94)) and -0.92 (-1.65, -0.19) respectively. Conclusions: In this ethnically diverse cohort, maternal adherence to a Mediterranean diet in early pregnancy was associated with favorable neurobehavioral outcomes in early childhood and with sex-dependent methylation differences of MEG3, IGF2, and SGCE/PEG10 DMRs.}, number={SEP}, journal={Frontiers in Cell and Developmental Biology}, author={House, John S. and Mendez, M. and Maguire, R.L. and Gonzalez-Nahm, S. and Huang, Z. and Daniels, J. and Murphy, S.K. and Fuemmeler, B.F. and Wright, F.A. and Hoyo, C.}, year={2018}, pages={107} }
 @article{golden_yu_meilleur_blakeley_duff_karton_vrielink_2017, title={An Extended n-h bond, driven by a conserved second-order interaction, orients the flavin n5 orbital in cholesterol oxidase}, volume={7}, journal={Scientific Reports}, author={Golden, E. and Yu, L. J. and Meilleur, F. and Blakeley, M. P. and Duff, A. P. and Karton, A. and Vrielink, A.}, year={2017} }
 @article{neelon_ostbye_bennett_kravitz_clancy_stroo_iversen_hoyo_2017, title={Cohort profile for the Nurture Observational Study examining associations of multiple caregivers on infant growth in the Southeastern USA}, volume={7}, number={2}, journal={BMJ Open}, author={Neelon, S. E. B. and Ostbye, T. and Bennett, G. G. and Kravitz, R. M. and Clancy, S. M. and Stroo, M. and Iversen, E. and Hoyo, C.}, year={2017} }
 @article{maguire_vidal_murphy_hoyo_2017, title={Disparities in cervical cancer incidence and mortality: Can epigenetics contribute to eliminating disparities?}, volume={133}, journal={Cancer disparities}, author={Maguire, R. L. and Vidal, A. C. and Murphy, S. K. and Hoyo, C.}, year={2017}, pages={129–156} }
 @article{gao_millstein_siegmund_dubeau_maguire_gilliland_murphy_hoyo_breton_2017, title={Epigenetic regulation of AXL and risk of childhood asthma symptoms}, volume={9}, journal={Clinical Epigenetics}, author={Gao, L. and Millstein, J. and Siegmund, K. D. and Dubeau, L. and Maguire, R. and Gilliland, F. D. and Murphy, S. K. and Hoyo, C. and Breton, C. V.}, year={2017} }
 @article{guerrios-rivera_howard_frank_de hoedt_beverly_grant_hoyo_freedland_2017, title={Is Body Mass Index the Best Adiposity Measure for Prostate Cancer Risk? Results From a Veterans Affairs Biopsy Cohort}, volume={105}, ISSN={["1527-9995"]}, DOI={10.1016/j.urology.2017.03.042}, abstractNote={Objective To test multiple adiposity measures and prostate cancer (PC) risk in men undergoing prostate biopsy. We hypothesized that body mass index (BMI), body fat, and waist circumference would be highly correlated, and all would be associated with aggressive PC, but not overall risk. Subjects and Methods A case (483)-control (496) study among men undergoing prostate biopsy from 2007 to 2016 was conducted at the Durham Veterans Affairs Medical Center. Anthropometric and self-reported measurements were taken. Percent body fat was measured. Associations between adiposity measures and PC risk and high-grade PC (Gleason ≥7) were examined using logistic regression. Results BMI, percent body fat, and waist circumference were highly correlated (ρ ≥ .79) (P < .001). On multivariable analysis, BMI (P = .011) was associated with overall PC risk, but percent body fat (P = .16) and waist circumference (P = .19) were not. However, all adiposity measurements were associated with high-grade disease (P < .001). We found a strong relationship between self-reported and measured weight (ρ = .97) and height (ρ = .92). Conclusion BMI, body fat, and waist circumference were all highly correlated and associated with aggressive PC. This study supports the idea that higher adiposity is selectively associated with high-grade PC and reinforces the continued use of self-reported BMI as a measure of obesity in epidemiologic studies of PC. To test multiple adiposity measures and prostate cancer (PC) risk in men undergoing prostate biopsy. We hypothesized that body mass index (BMI), body fat, and waist circumference would be highly correlated, and all would be associated with aggressive PC, but not overall risk. A case (483)-control (496) study among men undergoing prostate biopsy from 2007 to 2016 was conducted at the Durham Veterans Affairs Medical Center. Anthropometric and self-reported measurements were taken. Percent body fat was measured. Associations between adiposity measures and PC risk and high-grade PC (Gleason ≥7) were examined using logistic regression. BMI, percent body fat, and waist circumference were highly correlated (ρ ≥ .79) (P < .001). On multivariable analysis, BMI (P = .011) was associated with overall PC risk, but percent body fat (P = .16) and waist circumference (P = .19) were not. However, all adiposity measurements were associated with high-grade disease (P < .001). We found a strong relationship between self-reported and measured weight (ρ = .97) and height (ρ = .92). BMI, body fat, and waist circumference were all highly correlated and associated with aggressive PC. This study supports the idea that higher adiposity is selectively associated with high-grade PC and reinforces the continued use of self-reported BMI as a measure of obesity in epidemiologic studies of PC.}, journal={UROLOGY}, author={Guerrios-Rivera, Lourdes and Howard, Lauren and Frank, Jennifer and De Hoedt, Amanda and Beverly, Devon and Grant, Delores J. and Hoyo, Cathrine and Freedland, Stephen J.}, year={2017}, month={Jul}, pages={129–135} }
 @article{freedland_hoyo_turner_moorman_muller_faria_carvahal_reis_mauad_carvalho_et al._2017, title={MP92-09 Implications of Regionalizing Care in the Developing World: Impact of  Distance to Referral Center on Compliance to Biopsy Recommendations in a Brazilian Prostate Cancer Screening Cohort}, volume={197}, ISSN={0022-5347 1527-3792}, url={http://dx.doi.org/10.1016/J.JURO.2017.02.2870}, DOI={10.1016/J.JURO.2017.02.2870}, abstractNote={You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety II1 Apr 2017MP92-09 IMPLICATIONS OF REGIONALIZING CARE IN THE DEVELOPING WORLD: IMPACT OF DISTANCE TO REFERRAL CENTER ON COMPLIANCE TO BIOPSY RECOMMENDATIONS IN A BRAZILIAN PROSTATE CANCER SCREENING COHORT Alexis Freedland, Cathrine Hoyo, Elizabeth Turner, Patricia Moorman, Roberto Muller, Eliney Faria, Gustavo Carvahal, Rodolfo Reis, Edmundo Mauad, Andre Carvalho, and Stephen Freedland Alexis FreedlandAlexis Freedland More articles by this author , Cathrine HoyoCathrine Hoyo More articles by this author , Elizabeth TurnerElizabeth Turner More articles by this author , Patricia MoormanPatricia Moorman More articles by this author , Roberto MullerRoberto Muller More articles by this author , Eliney FariaEliney Faria More articles by this author , Gustavo CarvahalGustavo Carvahal More articles by this author , Rodolfo ReisRodolfo Reis More articles by this author , Edmundo MauadEdmundo Mauad More articles by this author , Andre CarvalhoAndre Carvalho More articles by this author , and Stephen FreedlandStephen Freedland More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2870AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In many developing countries, care is regionalized at a few high volume centers. However, unlike Western nations where high percentages live in urban areas, developing countries have a higher percent living in rural areas or small towns. It is unknown if the benefits of regionalization outweigh the barriers this creates for access. We tested the link between distance from screening site to biopsy (bx) referral center and risk of non-compliance with showing up to have a bx in a population-based PC screening cohort in Brazil. METHODS We reviewed records from 1,561 men recommended to undergo a bx after an initial PC screen by a medical mobile unit at their local clinic between 2004 and 2007. Bxs were performed at a regional referral center, Barretos Cancer Hospital (BCH). Clinical data between men who complied with the bx vs. not were compared with rank-sum & chi-square. Multivariable logistic regression analysis of distance from screening site to BCH (km) and risk of non-compliance was performed adjusting for age and year of screening. RESULTS Median distance was 257km (IQR 135-718). Non-compliant men were older (68 vs 66 yrs), had a higher PSA (4.9 vs 4.2), were less likely to have an abnormal DRE (20% vs 33%) and lived further from BCH (921 vs 225 km) (all p<0.001). On crude and multivariable analyses, further distance was significantly linked with bx non-compliance (OR/100km 0.83, p<0.001, see figure). Among men who lived within 150km of BCH, distance was unrelated to compliance (OR/100km 1.09, p=0.87). CONCLUSIONS In Brazil, where distances from PC screening to bx clinic can be hundreds of kms, greater distance to referral center was related to reduced compliance to bx. However, among men who lived within 150km, distance was unrelated to compliance. While regionalization of care may in theory improve quality, it comes at the cost of reduced compliance and thus reduced access and represents a significant barrier to optimal care if distances are large. In regards to PC screening and bx, our data suggest distances up to 150km do not create barriers for care. Alternative thresholds, however, may apply for other services and in other cultures. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1229-e1230 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Alexis Freedland More articles by this author Cathrine Hoyo More articles by this author Elizabeth Turner More articles by this author Patricia Moorman More articles by this author Roberto Muller More articles by this author Eliney Faria More articles by this author Gustavo Carvahal More articles by this author Rodolfo Reis More articles by this author Edmundo Mauad More articles by this author Andre Carvalho More articles by this author Stephen Freedland More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...}, number={4S}, journal={Journal of Urology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Freedland, Alexis and Hoyo, Cathrine and Turner, Elizabeth and Moorman, Patricia and Muller, Roberto and Faria, Eliney and Carvahal, Gustavo and Reis, Rodolfo and Mauad, Edmundo and Carvalho, Andre and et al.}, year={2017}, month={Apr} }
 @article{sharp_salas_monnereau_allard_yousefi_everson_bohlin_xu_huang_reese_et al._2017, title={Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium}, volume={26}, number={20}, journal={Human Molecular Genetics}, author={Sharp, G. C. and Salas, L. A. and Monnereau, C. and Allard, C. and Yousefi, P. and Everson, T. M. and Bohlin, J. and Xu, Z. L. and Huang, R. C. and Reese, S. E. and et al.}, year={2017}, pages={4067–4085} }
 @article{luo_mccullough_tzeng_darrah_vengosh_maguire_maity_samuel-hodge_murphy_mendez_et al._2017, title={Maternal blood cadmium, lead and arsenic levels, nutrient combinations, and offspring birthweight}, volume={17}, journal={BMC Public Health}, author={Luo, Y. W. and McCullough, L. E. and Tzeng, J. Y. and Darrah, T. and Vengosh, A. and Maguire, R. L. and Maity, A. and Samuel-Hodge, C. and Murphy, S. K. and Mendez, M. A. and et al.}, year={2017} }
 @article{mccullough_miller_calderwood_shivappa_steck_forman_mendez_maguire_fuemmeler_kollins_et al._2017, title={Maternal inflammatory diet and adverse pregnancy outcomes: Circulating cytokines and genomic imprinting as potential regulators?}, volume={12}, ISSN={["1559-2308"]}, DOI={10.1080/15592294.2017.1347241}, abstractNote={Excessive inflammation during pregnancy alters homeostatic mechanisms of the developing fetus and has been linked to adverse pregnancy outcomes. An anti-inflammatory diet could be a promising avenue to combat the pro-inflammatory state of pregnancy, particularly in obese women, but we lack mechanistic data linking this dietary pattern during pregnancy to inflammation and birth outcomes. In an ethnically diverse cohort of 1057 mother-child pairs, we estimated the relationships between dietary inflammatory potential [measured via the energy-adjusted dietary inflammatory index (E-DII™)] and birth outcomes overall, as well as by offspring sex and maternal pre-pregnancy body mass index (BMI). In a subset of women, we also explored associations between E-DII, circulating cytokines (n = 105), and offspring methylation (n = 338) as potential modulators of these relationships using linear regression. Adjusted regression models revealed that women with pro-inflammatory diets had elevated rates of preterm birth among female offspring [β = −0.22, standard error (SE) = 0.07, P<0.01], but not male offspring (β=0.09, SE = 0.06, P<0.12) (Pinteraction = 0.003). Similarly, we observed pro-inflammatory diets were associated with higher rates of caesarean delivery among obese women (β = 0.17, SE = 0.08, P = 0.03), but not among women with BMI <25 kg/m2 (Pinteraction = 0.02). We observed consistent inverse associations between maternal inflammatory cytokine concentrations (IL-12, IL-17, IL-4, IL-6, and TNFα) and lower methylation at the MEG3 regulatory sequence (P<0.05); however, results did not support the link between maternal E-DII and circulating cytokines. We replicate work by others on the association between maternal inflammatory diet and adverse pregnancy outcomes and provide the first empirical evidence supporting the inverse association between circulating cytokine concentrations and offspring methylation.}, number={8}, journal={EPIGENETICS}, author={McCullough, Lauren E. and Miller, Erline E. and Calderwood, Laura E. and Shivappa, Nitin and Steck, Susan E. and Forman, Michele R. and Mendez, Michelle A. and Maguire, Rachel and Fuemmeler, Bernard F. and Kollins, Scott H. and et al.}, year={2017}, pages={688–697} }
 @article{hoffman_butt_webster_preston_hammel_makey_lorenzo_cooper_carignan_meeker_et al._2017, title={Temporal Trends in Exposure to Organophosphate Flame Retardants in the United States}, volume={4}, ISSN={["2328-8930"]}, DOI={10.1021/acs.estlett.6b00475}, abstractNote={During the past decade, use of organophosphate compounds as flame retardants and plasticizers has increased. Numerous studies investigating biomarkers (i.e., urinary metabolites) demonstrate ubiquitous human exposure and suggest that human exposure may be increasing. To formally assess temporal trends, we combined data from 14 U.S. epidemiologic studies for which our laboratory group previously assessed exposure to two commonly used organophosphate compounds, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP). Using individual-level data and samples collected between 2002 and 2015, we assessed temporal and seasonal trends in urinary bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), the metabolites of TDCIPP and TPHP, respectively. Data suggest that BDCIPP concentrations have increased dramatically since 2002. Samples collected in 2014 and 2015 had BDCIPP concentrations that were more than 15 times higher than those collected in 2002 and 2003 (10β = 16.5; 95% confidence interval from 9.64 to 28.3). Our results also demonstrate significant increases in DPHP levels; however, increases were much smaller than for BDCIPP. Additionally, results suggest that exposure varies seasonally, with significantly higher levels of exposure in summer for both TDCIPP and TPHP. Given these increases, more research is needed to determine whether the levels of exposure experienced by the general population are related to adverse health outcomes.}, number={3}, journal={ENVIRONMENTAL SCIENCE & TECHNOLOGY LETTERS}, author={Hoffman, Kate and Butt, Craig M. and Webster, Thomas F. and Preston, Emma V. and Hammel, Stephanie C. and Makey, Colleen and Lorenzo, Amelia M. and Cooper, Ellen M. and Carignan, Courtney and Meeker, John D. and et al.}, year={2017}, month={Mar}, pages={112–118} }
 @article{zapata_howard_frank_simon_hoyo_grant_freedland_vidal_2017, title={The association between sexual function and prostate cancer risk in US veterans}, volume={19}, ISSN={["1745-7262"]}, DOI={10.4103/1008-682x.184869}, abstractNote={Sexual dysfunction and prostate cancer are common among older men. Few studies explored the association between these two illnesses. We examined whether sexual function is associated with prostate cancer risk among older men. Among 448 men undergoing prostate biopsy at the Durham Veterans Affairs Hospital, sexual function was ascertained from the Expanded Prostate Cancer Index Composite sexual assessment. We tested the link between sexual function and prostate cancer risk adjusting for multiple demographic and clinical characteristics using logistic regression. Multinomial logistic regression was used to test the associations with risk of low-grade (Gleason ≤6) and high-grade (Gleason ≥7 or ≥4 + 3) disease versus no cancer. Of 448 men, 209 (47%) had a positive biopsy; these men were less likely to be white (43% vs 55%, P = 0.013), had higher prostate-specific antigen (PSA) (6.0 vs 5.4 ng ml-1 , P < 0.001), but with lower mean sexual function score (47 vs 54, P = 0.007). There was no difference in age, BMI, pack years smoked, history of heart disease and/or diabetes. After adjusting for baseline differences, sexual function was linked with a decreased risk of overall prostate cancer risk (OR: 0.91 per 10-point change in sexual function, P = 0.004) and high-grade disease whether defined as Gleason ≥7 (OR: 0.86, P = 0.001) or ≥4 + 3 (OR: 0.85, P = 0.009). Sexual function was unrelated to low-grade prostate cancer (OR: 0.94, P = 0.13). Thus, among men undergoing prostate biopsy, higher sexual function was associated with a decreased risk of overall and high-grade prostate cancer. Confirmatory studies are needed.}, number={2}, journal={ASIAN JOURNAL OF ANDROLOGY}, author={Zapata, Daniel F. and Howard, Lauren E. and Frank, Jennifer and Simon, Ross M. and Hoyo, Cathrine and Grant, Delores J. and Freedland, Stephen J. and Vidal, Adriana C.}, year={2017}, pages={191–195} }
 @article{moylan_mavis_bashir_malik_bozdogan_buie_hoyo_diehl_murphy_abdelmalek_2017, title={Visceral and subcutaneous adipose tissue measurements associate with increased metabolic risk for NAFLD in pre-pubertal obese children}, volume={66}, journal={Hepatology}, author={Moylan, C. A. and Mavis, A. M. and Bashir, M. R. and Malik, D. and Bozdogan, E. and Buie, S. and Hoyo, C. and Diehl, A. M. and Murphy, S. K. and Abdelmalek, M. F.}, year={2017}, pages={665A–665} }
 @article{fuemmeler_wang_iversen_maguire_murphy_hoyo_2016, title={Association between Prepregnancy Body Mass Index and Gestational Weight Gain with Size, Tempo, and Velocity of Infant Growth: Analysis of the Newborn Epigenetic Study Cohort}, volume={12}, ISSN={["2153-2176"]}, DOI={10.1089/chi.2015.0253}, abstractNote={Background: The first 1000 days of life is a critical period of infant growth that has been linked to future adult health. Understanding prenatal factors that contribute to variation in growth during this period could inform successful prevention strategies. Methods: Prenatal and maternal characteristics, including prepregnancy obesity and gestational weight gain were evaluated in relation to weight growth trajectories during the first 24 months of life using the SuperImposition by Translation and Rotation (SITAR) method, which provides estimates of infant size, timing to peak velocity, and growth velocity. The study sample included 704 mother-infant dyads from a multiethnic prebirth cohort from the Southeastern United States. The total number of weight measures was 8670 (median number per child = 14). Results: Several prenatal and maternal characteristics were linked with infant growth parameters. The primary findings show that compared to women with a prepregnancy BMI between 18 and 24.9, women with a prepregnancy BMI ≥40 had infants that were 8% larger during the first 24 months, a delayed tempo of around 9 days, and a slower velocity. Mothers who had greater than adequate gestational weight gain had infants that were 5% larger even after controlling for prepregnancy BMI and several other covariates. Conclusions: The findings contribute new data on the associations between gestational weight gain and aspects of early growth using the SITAR method, and support a growing consensus in the literature that both prepregnancy BMI and gestational weight gain relate independently to risk for greater postnatal weight growth.}, number={3}, journal={CHILDHOOD OBESITY}, author={Fuemmeler, Bernard F. and Wang, Lin and Iversen, Edwin S. and Maguire, Rachel and Murphy, Susan K. and Hoyo, Cathrine}, year={2016}, month={Jun}, pages={210–218} }
 @article{joubert_felix_yousefi_bakulski_just_breton_reese_markunas_richmond_xu_et al._2016, title={DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis}, volume={98}, ISSN={0002-9297}, url={http://dx.doi.org/10.1016/J.AJHG.2016.02.019}, DOI={10.1016/J.AJHG.2016.02.019}, abstractNote={Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10−16). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure. Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10−16). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure. Despite years of advisories regarding health risks to the developing fetus from maternal smoking, many pregnant women still smoke, including 12.3% in the US.1Tong V.T. Dietz P.M. Morrow B. D’Angelo D.V. Farr S.L. Rockhill K.M. England L.J. Centers for Disease Control and Prevention (CDC)Trends in smoking before, during, and after pregnancy--Pregnancy Risk Assessment Monitoring System, United States, 40 sites, 2000-2010.MMWR Surveill. Summ. 2013; 62: 1-19PubMed Google Scholar Maternal smoking during pregnancy is regarded as a cause of low birth weight, reduced pulmonary function (PLF [MIM: 608852]), orofacial clefts (OFC1 [MIM: 119530]), and sudden infant death syndrome (SIDS [MIM: 272120]) in exposed newborns.2US Department of Health and Human ServicesThe health consequences of smoking—50 years of progress: A report of the surgeon general. US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, Atlanta, GA2014Google Scholar Other adverse birth outcomes3Moritsugu K.P. The 2006 Report of the Surgeon General: the health consequences of involuntary exposure to tobacco smoke.Am. J. Prev. Med. 2007; 32: 542-543Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar have been associated with maternal smoking in pregnancy, along with common health problems in children, including asthma (ASRT [MIM: 600807]), otitis media (OMS [MIM: 166760]), and neurobehavioral disorders.2US Department of Health and Human ServicesThe health consequences of smoking—50 years of progress: A report of the surgeon general. US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, Atlanta, GA2014Google Scholar The mechanisms for the adverse health effects of maternal smoking during pregnancy on offspring remain poorly understood.2US Department of Health and Human ServicesThe health consequences of smoking—50 years of progress: A report of the surgeon general. US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, Atlanta, GA2014Google Scholar Recently, studies have examined the potential role of epigenetic modifications such as DNA methylation at specific CpG sites (CpGs). These include studies examining genome-wide DNA methylation in newborns in relation to maternal smoking in pregnancy with the Illumina Infinium HumanMethylation27 (27K) BeadChip4Breton C.V. Siegmund K.D. Joubert B.R. Wang X. Qui W. Carey V. Nystad W. Håberg S.E. Ober C. Nicolae D. et al.Asthma BRIDGE consortiumPrenatal tobacco smoke exposure is associated with childhood DNA CpG methylation.PLoS ONE. 2014; 9: e99716Crossref PubMed Scopus (94) Google Scholar, 5Flom J.D. Ferris J.S. Liao Y. Tehranifar P. Richards C.B. Cho Y.H. Gonzalez K. Santella R.M. Terry M.B. Prenatal smoke exposure and genomic DNA methylation in a multiethnic birth cohort. Cancer Epidemiol.Biomarkers Prev. 2011; 20: 2518-2523Crossref PubMed Scopus (76) Google Scholar, 6Suter M. Ma J. Harris A. Patterson L. Brown K.A. Shope C. Showalter L. Abramovici A. Aagaard-Tillery K.M. Maternal tobacco use modestly alters correlated epigenome-wide placental DNA methylation and gene expression.Epigenetics. 2011; 6: 1284-1294Crossref PubMed Scopus (212) Google Scholar or the newer platform with wider coverage, the HumanMethylation450 (450K) BeadChip.7Joubert B.R. Håberg S.E. Nilsen R.M. Wang X. Vollset S.E. Murphy S.K. Huang Z. Hoyo C. Midttun Ø. Cupul-Uicab L.A. et al.450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy.Environ. Health Perspect. 2012; 120: 1425-1431Crossref PubMed Scopus (543) Google Scholar, 8Markunas C.A. Xu Z. Harlid S. Wade P.A. Lie R.T. Taylor J.A. Wilcox A.J. Identification of DNA methylation changes in newborns related to maternal smoking during pregnancy.Environ. Health Perspect. 2014; 122: 1147-1153PubMed Google Scholar, 9Richmond R.C. Simpkin A.J. Woodward G. Gaunt T.R. Lyttleton O. McArdle W.L. Ring S.M. Smith A.D. Timpson N.J. Tilling K. et al.Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC).Hum. Mol. Genet. 2015; 24: 2201-2217Crossref PubMed Scopus (247) Google Scholar, 10Küpers L.K. Xu X. Jankipersadsing S.A. Vaez A. la Bastide-van Gemert S. Scholtens S. Nolte I.M. Richmond R.C. Relton C.L. Felix J.F. et al.DNA methylation mediates the effect of maternal smoking during pregnancy on birthweight of the offspring.Int. J. Epidemiol. 2015; 44: 1224-1237Crossref PubMed Scopus (133) Google Scholar A number of differentially methylated loci have been identified in offspring in relation to maternal smoking in pregnancy in individual studies (references in the Supplemental Note). One study examined the top CpGs with respect to timing of exposure and found that the signals reflect sustained, rather than short-term, exposure to maternal smoking during pregnancy,11Joubert B.R. Haberg S.E. Bell D.A. Nilsen R.M. Vollset S.E. Midttun O. Ueland P.M. Wu M.C. Nystad W. Peddada S.D. et al.Maternal smoking and DNA methylation in newborns: in utero effect or epigenetic inheritance.Cancer Epidemiol. Biomarkers Prev. 2014; 23: 1007-1017Crossref PubMed Scopus (92) Google Scholar but this has not been evaluated genome-wide. A few studies suggest that some of these methylation signals persist into later childhood and adolescence, but data are limited.9Richmond R.C. Simpkin A.J. Woodward G. Gaunt T.R. Lyttleton O. McArdle W.L. Ring S.M. Smith A.D. Timpson N.J. Tilling K. et al.Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC).Hum. Mol. Genet. 2015; 24: 2201-2217Crossref PubMed Scopus (247) Google Scholar, 12Lee K.W. Richmond R. Hu P. French L. Shin J. Bourdon C. Reischl E. Waldenberger M. Zeilinger S. Gaunt T. et al.Prenatal exposure to maternal cigarette smoking and DNA methylation: epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age.Environ. Health Perspect. 2015; 123: 193-199PubMed Google Scholar The combination of genome-wide data across studies via meta-analysis to generate large sample sizes for the discovery of loci that would not have been identified from individual studies has been very successful in genetics, but this approach has rarely been used with methylation data. To address the impact of maternal smoking during pregnancy on newborns with much greater power, we recruited 13 birth cohort studies with data on maternal smoking during pregnancy and DNA methylation in offspring from the 450K BeadChip into the Pregnancy and Childhood Epigenetics consortium (PACE). We meta-analyzed harmonized cohort-specific associations between maternal smoking during pregnancy and DNA methylation in the offspring. We examined both sustained maternal smoking and any smoking during pregnancy. We also examined persistence of DNA methylation patterns related to maternal smoking in newborns among older children, including adjustment for postnatal secondhand tobacco smoke exposure. For functional follow-up of findings, we evaluated the associations between methylation status in the newly identified CpGs and expression levels of nearby genes and performed pathway and functional network analyses. This study represents a large and comprehensive evaluation of the impact of maternal smoking during pregnancy on DNA methylation in offspring. A total of 13 PACE cohorts participated in the meta-analysis of maternal smoking during pregnancy and 450K DNA methylation in newborns. These studies, listed in alphabetical order, are the Avon Longitudinal Study of Parents and Children (ALSPAC), the Center for Health Assessment of Mothers and Children of Salinas (CHAMACOS), the Children’s Health Study (CHS), the GECKO Drenthe cohort, the Generation R Study, Isle of Wight (IOW), Mechanisms of the Development of Allergy (MeDALL), three independent datasets from the Norwegian Mother and Child Cohort Study (MoBa1, MoBa2, and MoBa3), the Norway Facial Clefts Study (NFCS), the Newborn Epigenetics Study (NEST), and Project Viva. MeDALL represents a pooled analysis of four cohorts with coordinated methylation measurements: Infancia y Medio Ambiente (INMA), Etudes des Déterminants pré et postnatals précoces du développement et de la santé de l’Enfant (EDEN), Children’s Allergy Environment Stockholm Epidemiology study (BAMSE), and Prevention and Incidence of Asthma and Mite Allergy (PIAMA). Two of the MeDALL cohorts contributed to the newborn meta-analysis (INMA and EDEN). There were five studies with data on older children: ALSPAC, Genes-environments and Admixture in Latino Americans (GALA II), the Study to Explore Early Development (SEED), MeDALL (INMA, EDEN, BAMSE, and PIAMA), and an independent methylation dataset from BAMSE subjects. Ethical approval for study protocols was obtained for all participating cohorts. Further information on this as well as the study methods for each cohort are described in detail in the Supplemental Note. For this paper, participating cohorts shared only results files from in-house analyses. No individual data were shared for this paper. Therefore, access to the individual cohort-level data for the purpose of reproducing results would require individual data transfer agreements to be negotiated with and approved by each of the contributing cohorts. Cohorts assessed maternal smoking during pregnancy via questionnaires completed by the mothers. The MoBa study (MoBa1 and MoBa2) also used cotinine measurements from maternal blood samples taken during pregnancy as part of the definition of maternal smoking during pregnancy. More details on the cohort-specific smoking variables are in the Supplemental Note. In a previous publication from the MoBa1 study, significant associations between maternal smoking during pregnancy and DNA methylation in newborns were driven not by transient smoking that ended early in pregnancy but rather by sustained smoking during pregnancy.11Joubert B.R. Haberg S.E. Bell D.A. Nilsen R.M. Vollset S.E. Midttun O. Ueland P.M. Wu M.C. Nystad W. Peddada S.D. et al.Maternal smoking and DNA methylation in newborns: in utero effect or epigenetic inheritance.Cancer Epidemiol. Biomarkers Prev. 2014; 23: 1007-1017Crossref PubMed Scopus (92) Google Scholar Thus, each cohort ran separate models to evaluate both sustained smoking and any smoking during pregnancy. The variable (yes/no) for sustained smoking during pregnancy was designed to capture women who smoked at least one cigarette per day through most of pregnancy. To cleanly contrast the effect of sustained smoking through pregnancy with that of never smoking during pregnancy, we excluded women who reported quitting smoking during pregnancy from the sustained smoking models. The variable (yes/no) for any maternal smoking during pregnancy was designed to capture any amount of smoking during pregnancy, at any time, even if a woman reported quitting. Because we did not exclude women who quit smoking during pregnancy from the models representing any smoking during pregnancy, the total sample sizes are slightly larger than those of the models representing sustained smoking during pregnancy. Genome-wide analyses use large sample statistics. We limited meta-analyses to cohorts with at least 15 subjects in both the exposed and unexposed groups. This excluded four cohorts (CHAMACOS, CHS, IOW, and Project Viva) from the sustained smoking models. However these cohorts did participate in the meta-analysis of any smoking during pregnancy. Each cohort independently conducted laboratory measurements and quality control. The samples for each cohort underwent bisulfite conversion via the EZ-96 DNA Methylation kit (Zymo Research). Samples were processed with the Illumina Infinium HumanMethylation450 (450K) BeadChip (Illumina) at Illumina or in cohort-specific laboratories. Quality control of samples was performed by each cohort and failed samples were excluded on the basis of Illumina’s detection p value, low sample DNA concentration, sample call rate, CpG-specific percentage of missing values, bisulfite conversion efficiency, gender verification with multidimensional scaling plots, and other quality control metrics specific to cohorts. Cohorts could also use validated, published statistical methods for normalizing their methylation data on the untransformed methylation beta values (ranging from 0 to 1). Some cohorts also made independent probe exclusions. More details are provided in the Supplemental Note. For the meta-analysis, additional probe exclusions were made across all cohorts. Specifically, we excluded control probes (n = 65), probes that mapped to the X (n = 11,232) or Y (n = 416) chromosomes, probes with an underlying SNP mapping to the last five nucleotides of the probe sequence (N = 9,168) as previously described,7Joubert B.R. Håberg S.E. Nilsen R.M. Wang X. Vollset S.E. Murphy S.K. Huang Z. Hoyo C. Midttun Ø. Cupul-Uicab L.A. et al.450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy.Environ. Health Perspect. 2012; 120: 1425-1431Crossref PubMed Scopus (543) Google Scholar and CpGs with an implausible (zero) value for the SE (n = 67). This left a total of 464,628 CpGs included in the meta-analysis. Each cohort ran independent statistical analyses according to a common pre-specified analysis plan. Robust linear regression was used in R13R Core TeamR: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria2013http://www.R-project.org/Google Scholar to evaluate the association between maternal smoking during pregnancy and cord blood DNA methylation for each probe while accounting for potential heteroskedasticity and/or influential outliers. Each cohort ran the following covariate-adjusted statistical models: (1) the primary model, which used sustained maternal smoking during pregnancy as the exposure and the normalized betas as the outcome, (2) sustained maternal smoking during pregnancy as the exposure and raw betas (not normalized) as the outcome, (3) any maternal smoking during pregnancy as the exposure and normalized betas as the outcome, (4) any maternal smoking during pregnancy as the exposure and raw betas as the outcome, and (5) sustained maternal smoking during pregnancy as the exposure and normalized betas as the outcome, with additional adjustment for cell type proportion. All models were adjusted for maternal age, maternal education (or a surrogate socioeconomic metric), parity, and technical covariates such as batch or plate. Some cohorts used ComBat14Leek J.T. Johnson W.E. Parker H.S. Jaffe A.E. Storey J.D. The sva package for removing batch effects and other unwanted variation in high-throughput experiments.Bioinformatics. 2012; 28: 882-883Crossref PubMed Scopus (2291) Google Scholar to account for batch effects and therefore did not include batch or plate as covariates in the models with normalized betas (see Supplemental Note). Additional correction for study design or sampling factors was done as needed in some cohorts. Because maternal smoking during pregnancy is not related to the child’s sex, it cannot be a confounder and thus was not included in models. We did not adjust for principal components (PCs) because not all cohorts had genome-wide genotype data and cohorts with genotype data had it only for a subset of subjects with methylation data. Furthermore, in one large cohort with PC data, models adjusted for PCs showed little variation in the results (correlation of betas = 0.991; correlation of log(p values) = 0.996) when compared to models without this adjustment, despite a reduction in sample size. The statistical models for cohorts with DNA methylation measured in older children were the same, with the additional adjustment for second-hand tobacco smoke exposure. All cohorts independently estimated cell type proportion by using the reference-based Houseman method15Houseman E.A. Accomando W.P. Koestler D.C. Christensen B.C. Marsit C.J. Nelson H.H. Wiencke J.K. Kelsey K.T. DNA methylation arrays as surrogate measures of cell mixture distribution.BMC Bioinformatics. 2012; 13: 86Crossref PubMed Scopus (1902) Google Scholar in the minfi package16Aryee M.J. Jaffe A.E. Corrada-Bravo H. Ladd-Acosta C. Feinberg A.P. Hansen K.D. Irizarry R.A. Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays.Bioinformatics. 2014; 30: 1363-1369Crossref PubMed Scopus (2066) Google Scholar with the Reinius et al. dataset for reference.17Reinius L.E. Acevedo N. Joerink M. Pershagen G. Dahlén S.E. Greco D. Söderhäll C. Scheynius A. Kere J. Differential DNA methylation in purified human blood cells: implications for cell lineage and studies on disease susceptibility.PLoS ONE. 2012; 7: e41361Crossref PubMed Scopus (708) Google Scholar Cell type correction was applied by inclusion of the six estimated cell type proportions (CD8T, CD4T, NK cells, B cells, monocytes, granulocytes) as covariates in cohort-specific statistical models. We performed inverse variance-weighted fixed-effects meta-analysis with METAL.18Willer C.J. Li Y. Abecasis G.R. METAL: fast and efficient meta-analysis of genomewide association scans.Bioinformatics. 2010; 26: 2190-2191Crossref PubMed Scopus (2615) Google Scholar We accounted for multiple testing by controlling the false discovery rate (FDR) at 5%, implementing the method by Benjamini and Hochberg.19Benjamini Y. Hochberg Y. Controlling for False Discovery Rate: a Practical and Powerful Approach to Multiple Testing.J. R. Stat. Soc. Ser. B. 1995; 57: 289-300Google Scholar This method was applied to all instances of FDR correction described in this paper unless otherwise specified. CpGs with an FDR-corrected p value less than 0.05 were considered statistically significant. CpGs that were statistically significant based on the more stringent Bonferroni correction (uncorrected p value < 1.08 × 10−7 to account for 464,628 tests) were also noted. To determine the robustness of our models and findings, we performed an additional analysis in which we removed the cohorts of non-European ancestry (Table S1). We compared the effect estimates, SEs, and the distribution of the p values for the model to the estimates for our primary model to evaluate the consistency of our findings. The FDR-significant CpGs identified in the primary model from the newborn meta-analyses were followed up with a lookup replication approach in the results from five older children cohorts, and FDR correction was applied to account for the number of CpGs tested. We performed a systematic literature review to determine which CpGs represented findings not previously related to smoking exposure and methylation in the literature. A query of NCBI’s PubMed database was performed with the search terms ((“DNA Methylation”[Mesh] OR methylation) AND (“Smoking”[Mesh] OR smoking)) in order to be broad enough to capture all past studies reporting such results. CpGs with previously reported associations with smoking, both from prenatal exposure or in adults, were considered. This search yielded 789 results when performed on March 1, 2015. All results were then reviewed by title and abstract to determine whether they met inclusion criteria. First, results were limited to those performed in healthy human populations. That is, participants could not exclusively have been drawn from disease cases and studies could not have been performed only in cell lines or animals. Case-control analyses that included healthy controls were accepted as meeting this criterion, and no limitation was applied concerning the tissue used for DNA extraction. Second, studies were required to have performed DNA methylation analysis agnostically on a large scale as opposed to targeted interrogation of candidate CpGs. This was operationalized by including only analyses that examined >1,000 sites simultaneously. The Illumina 450K, 27K, and GoldenGate arrays all met this criterion. Third, the exposure was restricted to tobacco cigarette smoking. Related exposures, such as to other forms of tobacco use or smoke exposure, were not included. Lastly, studies had to have reported their significant results publicly. Studies that failed to report p values or gene annotations were excluded. Review of the existing literature on the effect of smoking on DNA methylation identified 25 publications meeting inclusion criteria. Of these, 16 studies reported results for adult smoking exposure,20Besingi W. Johansson A. Smoke-related DNA methylation changes in the etiology of human disease.Hum. Mol. Genet. 2014; 23: 2290-2297Crossref PubMed Scopus (132) Google Scholar, 21Breitling L.P. Yang R. Korn B. Burwinkel B. Brenner H. Tobacco-smoking-related differential DNA methylation: 27K discovery and replication.Am. J. Hum. 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 @article{joubert_felix_yousefi_bakulski_just_breton_reese_markunas_richmond_xu_et al._2016, title={DNA methylation in newborns and maternal smoking in pregnancy: Genome-wide consortium meta-analysis}, volume={98}, number={4}, journal={American Journal of Human Genetics}, author={Joubert, B. R. and Felix, J. F. and Yousefi, P. and Bakulski, K. M. and Just, A. C. and Breton, C. and Reese, S. E. and Markunas, C. A. and Richmond, R. C. and Xu, C. J. and et al.}, year={2016}, pages={680–696} }
 @article{skaar_murphy_hoyo_2016, title={Effects of Environmentally Acquired Heavy Metals and Nutrients on the Epigenome and Phenotype}, ISBN={["978-3-319-27447-8"]}, ISSN={["2168-4219"]}, DOI={10.1007/978-3-319-27449-2_5}, abstractNote={Cadmium, arsenic, mercury and lead are ubiquitous environmental contaminants that tend to co-occur. Unlike organic compounds that are chemically, biologically, or photo-degraded, these metals persist in the environment for indefinite periods. Although protein disruption/misfolding, generation of oxidative stress, and endocrine disruption are known effects of toxic metal exposure, beyond the known toxic effects of high dose exposure, mechanisms causing these effects, especially at low chronic doses, are still largely unknown. Epigenetics is emerging as a viable mechanistic framework to explain how the environment interacts with the genome to alter disease risk. Alterations in DNA methylation, histone marks and chromatin structure have been proposed as useful exposure assessment biomarkers that can substantially improve assessment of risk in etiologic studies where exposure occurs early during the life course. If developed into exposure-specific biomarkers, these epigenetic marks can be a powerful tool to identify populations exposed to low doses where phenotypic response may not be immediately apparent, and also to evaluate the efficacy of therapeutic and public health interventions. This could be particularly important as exposed populations tend to be the socioeconomically disadvantaged who have limited contact with the health care system. In this review, we provide an overview of the current state of literature on heavy-metal-associated epigenetic alterations. We discuss the extent to which such epigenetic alterations alter susceptibility to common chronic diseases and how they might be mitigated by some nutrients, albeit within narrow margins. We conclude by discussing key issues that must be resolved if human epigenetic data is to provide useful biomarkers and mechanistic insights into how low dose chronic exposure to these metals might alter the epigenome and increase disease susceptibility.}, journal={TRANSLATIONAL TOXICOLOGY: DEFINING A NEW THERAPEUTIC DISCIPLINE}, author={Skaar, David A. and Murphy, Susan K. and Hoyo, Cathrine}, year={2016}, pages={139–169} }
 @article{skaar_jirtle_hoyo_2016, title={Environmentally Induced Alterations in the Epigenome Affecting Obesity and Cancer in Minority Populations}, ISBN={["978-3-319-41608-3"]}, DOI={10.1007/978-3-319-41610-6_5}, abstractNote={The obesity epidemic of the last 30–40 years is may be linked to increased environmental chemical exposures with endocrine disrupting potential. The increases in obesity prevalence and severity coincide with increases in several adenocarcinomas at a time when cancer incidence has been generally declining, with disproportionate effects in different ethnic groups. Despite demonstrated associations between such exposures with obesity, and obesity with these cancers, an association between exposure to these environmental chemicals and adenocarcinomas has been difficult to demonstrate in part due to limits in exposure assessment. Exposure to these compounds elicits stable epigenetic responses; thus, if these alterations to the epigenome can be fully characterized, they can be exploited to improve exposure ascertainment. We summarize in this chapter evidence for the influence of environmental exposures on obesity and how epigenetic alterations may contribute to cancers that disproportionately affect minority populations exhibit disparities in incidence and mortality.}, journal={EPIGENETICS, ENERGY BALANCE, AND CANCER}, author={Skaar, David A. and Jirtle, Randy L. and Hoyo, Cathrine}, year={2016}, pages={109–146} }
 @article{li_xie_murphy_skaar_nye_vidal_cecil_dietrich_puga_jirtle_et al._2016, title={Lead Exposure during Early Human Development and DNA Methylation of Imprinted Gene Regulatory Elements in Adulthood}, volume={124}, ISSN={["1552-9924"]}, DOI={10.1289/ehp.1408577}, abstractNote={Lead exposure during early development causes neurodevelopmental disorders by unknown mechanisms. Epidemiologic studies have focused recently on determining associations between lead exposure and global DNA methylation; however, such approaches preclude the identification of loci that may alter human disease risk.The objective of this study was to determine whether maternal, postnatal, and early childhood lead exposure can alter the differentially methylated regions (DMRs) that control the monoallelic expression of imprinted genes involved in metabolism, growth, and development.Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study from birth to 78 months. When participants were adults, we used Sequenom EpiTYPER assays to test peripheral blood DNA to quantify CpG methylation in peripheral blood leukocytes at DMRs of 22 human imprinted genes. Statistical analyses were conducted using linear regression.Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation (β = -0.0014; 95% CI: -0.0023, -0.0005, p = 0.002), stronger in males (β = -0.0024; 95% CI: -0.0038, -0.0009, p = 0.003) than in females (β = -0.0009; 95% CI: -0.0020, 0.0003, p = 0.1). Elevated mean childhood blood lead concentration was also associated with a significant decrease in IGF2/H19 (β = -0.0013; 95% CI: -0.0023, -0.0003, p = 0.01) DMR methylation, but primarily in females, (β = -0.0017; 95% CI: -0.0029, -0.0006, p = 0.005) rather than in males, (β = -0.0004; 95% CI: -0.0023, 0.0015, p = 0.7). Elevated blood lead concentration during the neonatal period was associated with higher PLAGL1/HYMAI DMR methylation regardless of sex (β = 0.0075; 95% CI: 0.0018, 0.0132, p = 0.01). The magnitude of associations between cumulative lead exposure and CpG methylation remained unaltered from 30 to 78 months.Our findings provide evidence that early childhood lead exposure results in sex-dependent and gene-specific DNA methylation differences in the DMRs of PEG3, IGF2/H19, and PLAGL1/HYMAI in adulthood.Li Y, Xie C, Murphy SK, Skaar D, Nye M, Vidal AC, Cecil KM, Dietrich KN, Puga A, Jirtle RL, Hoyo C. 2016. Lead exposure during early human development and DNA methylation of imprinted gene regulatory elements in adulthood. Environ Health Perspect 124:666-673; http://dx.doi.org/10.1289/ehp.1408577.}, number={5}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Li, Yue and Xie, Changchun and Murphy, Susan K. and Skaar, David and Nye, Monica and Vidal, Adriana C. and Cecil, Kim M. and Dietrich, Kim N. and Puga, Alvaro and Jirtle, Randy L. and et al.}, year={2016}, month={May}, pages={666–673} }
 @article{mccullough_miller_mendez_murtha_murphy_hoyo_2016, title={Maternal B vitamins: effects on offspring weight and DNA methylation at genomically imprinted domains}, volume={8}, journal={Clinical Epigenetics}, author={McCullough, L. E. and Miller, E. E. and Mendez, M. A. and Murtha, A. P. and Murphy, S. K. and Hoyo, C.}, year={2016} }
 @article{king_kane_scarbrough_hoyo_murphy_2016, title={Neighborhood and Family Environment of Expectant Mothers May Influence Prenatal Programming of Adult Cancer Risk: Discussion and an Illustrative DNA Methylation Example}, volume={62}, ISSN={["1948-5573"]}, DOI={10.1080/19485565.2015.1126501}, abstractNote={Childhood stressors including physical abuse predict adult cancer risk. Prior research portrays this finding as an indirect mechanism that operates through coping behaviors, including adult smoking, or through increased toxic exposures during childhood. Little is known about potential direct causal mechanisms between early-life stressors and adult cancer. Because prenatal conditions can affect gene expression by altering DNA methylation, with implications for adult health, we hypothesize that maternal stress may program methylation of cancer-linked genes during gametogenesis. To illustrate this hypothesis, we related maternal social resources to methylation at the imprinted MEG3 differentially methylated regulatory region, which has been linked to multiple cancer types. Mothers (n = 489) from a diverse birth cohort (Durham, North Carolina) provided newborns’ cord blood and completed a questionnaire. Newborns of currently married mothers showed lower (−0.321 SD, p < .05) methylation compared to newborns of never-married mothers, who did not differ from newborns whose mothers were cohabiting and others (adjusted for demographics). MEG3 DNA methylation levels were also lower when maternal grandmothers co-resided before pregnancy (−0.314 SD, p < .05). A 1-SD increase in prenatal neighborhood disadvantage also predicted higher methylation (−0.137 SD, p < .05). In conclusion, we found that maternal social resources may result in differential methylation of MEG3, which demonstrates a potential partial mechanism priming socially disadvantaged newborns for later risk of some cancers.}, number={1}, journal={BIODEMOGRAPHY AND SOCIAL BIOLOGY}, author={King, Katherine E. and Kane, Jennifer B. and Scarbrough, Peter and Hoyo, Cathrine and Murphy, Susan K.}, year={2016}, month={Jan}, pages={87–104} }
 @article{soubry_guo_huang_hoyo_romanus_price_murphy_2016, title={Obesity-related DNA methylation at imprinted genes in human sperm: Results from the TIEGER study}, volume={8}, journal={Clinical Epigenetics}, author={Soubry, A. and Guo, L. S. and Huang, Z. Q. and Hoyo, C. and Romanus, S. and Price, T. and Murphy, S. K.}, year={2016} }
 @article{mccullough_mendez_miller_murtha_murphy_hoyo_2015, title={Associations between prenatal physical activity, birth weight, and DNA methylation at genomically imprinted domains in a multiethnic newborn cohort}, volume={10}, ISSN={["1559-2308"]}, DOI={10.1080/15592294.2015.1045181}, abstractNote={Birth weight is a commonly used indicator of the fetal environment and a predictor of future health outcomes. While the etiology of birth weight extremes is likely multifactorial, epidemiologic data suggest that prenatal physical activity (PA) may play an important role. The mechanisms underlying this association remain unresolved, although epigenetics has been proposed. This study aimed to estimate associations between prenatal PA, birth weight, and newborn DNA methylation levels at differentially methylated regions (DMRs) regulating 4 imprinted genes known to be important in fetal development. Study participants (N = 1281) were enrolled as part of the Newborn Epigenetics Study. Prenatal PA was ascertained using the Pregnancy Physical Activity Questionnaire, and birth weight data obtained from hospital records. Among 484 term mother-infant pairs, imprinted gene methylation levels were measured at DMRs using bisulfite pyrosequencing. Generalized linear and logistic regression models were used to estimate associations. After adjusting for preterm birth and race/ethnicity, we found that infants born to mothers in the highest quartile of total non-sedentary time had lower birth weight compared to infants of mothers in the lowest quartile (β = -81.16, SE = 42.02, P = 0.05). These associations appeared strongest among male infants (β = -125.40, SE = 58.10, P = 0.03). Methylation at the PLAGL1 DMR was related to total non-sedentary time (P < 0.05). Our findings confirm that prenatal PA is associated with reduced birth weight, and is the first study to support a role for imprinted gene plasticity in these associations. Larger studies are required.}, number={7}, journal={EPIGENETICS}, author={McCullough, Lauren E. and Mendez, Michelle A. and Miller, Erline E. and Murtha, Amy P. and Murphy, Susan K. and Hoyo, Cathrine}, year={2015}, month={Jul}, pages={597–606} }
 @article{neelon_stroo_mayhew_maselko_hoyo_2015, title={Correlation between maternal and infant cortisol varies by breastfeeding status}, volume={40}, ISSN={["1879-0453"]}, DOI={10.1016/j.infbeh.2015.06.005}, abstractNote={The objective of this study was to examine associations of mother and infant salivary cortisol, measured three times over the course of a day, and assess whether these varied by breastfeeding status.We conducted a cross-sectional study of 54 mothers and their infants aged 4-11 months. Mothers collected their own saliva and that of their infants upon awakening, 30min after waking and at bedtime. Breastfeeding status was reported by mothers and cortisol level was measured in saliva in μg/dl using standard techniques. We used generalized linear models to evaluate relationships between maternal and infant cortisol levels, and assessed whether the relationship differed by breastfeeding status: formula only compared to partial and full breastfeeding, adjusting for infant sex, race, age, maternal education, and family income.Thirty-four infants received formula only and 20 were either partially or fully breastfed. Breastfeeding was associated with higher household income, higher maternal education, and white race. Cortisol levels were higher among breastfed infants at all three time points. After adjustment, maternal cortisol levels were related with infant cortisol at bedtime only (regression estimate 0.06; 95% CI: 0.10, 1.1; p=0.02). The adjusted association between bedtime maternal and infant cortisol was stronger among breastfeeding dyads than among formula-feeding dyads (regression estimate 1.0; 95% CI: 0.1, 2.0; p=0.04 vs. 0.6; CI: -0.1, 1.3; p=0.10). In addition, we assessed the influence of maternal education and household income in our adjusted model; income strengthened the observed association, whereas maternal education did not change the estimate.Breastfeeding mothers and infants had significant correlations for cortisol at bedtime, while formula-feeding dyads did not. These data suggest that several factors may contribute to cortisol synchrony observed in mother/infant dyads, including the transfer of cortisol in human milk, physical interaction such as skin-to-skin contact, and shared environment. In addition, our findings support household income as a possible contributor.}, journal={INFANT BEHAVIOR & DEVELOPMENT}, author={Neelon, Sara E. Benjamin and Stroo, Marissa and Mayhew, Meghan and Maselko, Joanna and Hoyo, Cathrine}, year={2015}, month={Aug}, pages={252–258} }
 @article{king_murphy_hoyo_2015, title={Epigenetic regulation of Newborns' imprinted genes related to gestational growth: patterning by parental race/ethnicity and maternal socioeconomic status}, volume={69}, ISSN={["1470-2738"]}, DOI={10.1136/jech-2014-204781}, abstractNote={<h3>Background</h3> Children born to parents with lower income and education are at risk for obesity and later-life risk of common chronic diseases, and epigenetics has been hypothesised to link these associations. However, epigenetic targets are unknown. We focus on a cluster of well-characterised genomically imprinted genes because their monoallelic expression is regulated by DNA methylation at differentially methylated regions (DMRs), are critical in fetal growth, and DNA methylation patterns at birth have been associated with increased risk of birth weight extremes and overweight status or obesity in early childhood. <h3>Methods</h3> We measured DNA methylation at DMRs regulating genomically imprinted domains (<i>IGF2/H19</i>, <i>DLK1/MEG3</i>, <i>NNAT</i> and <i>PLAGL1</i>) using umbilical cord blood leucocytes from 619 infants recruited in Durham, North Carolina in 2010–2011. We examined differences in DNA methylation levels by race/ethnicity of both parents, and the role that maternal socioeconomic status (SES) may play in the association between race/ethnic epigenetic differences. <h3>Results</h3> Unadjusted race/ethnic differences only were evident for DMRs regulating <i>MEG3</i> and <i>IGF2</i>; race/ethnic differences persisted in <i>IGF2/H19</i> and <i>NNAT</i> after accounting for income and education. <h3>Conclusions</h3> Results suggest that parental factors may not only influence DNA methylation, but also do so in ways that vary by DMR. Findings support the hypothesis that epigenetics may link the observed lower SES during the prenatal period and poor outcomes such as low birth weight; lower birth weight has previously been associated with adult-onset chronic diseases and conditions that include cardiovascular diseases, diabetes, obesity and some cancers.}, number={7}, journal={JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH}, author={King, Katherine and Murphy, Susan and Hoyo, Cathrine}, year={2015}, month={Jul}, pages={639–647} }
 @article{murphy_erginer_huang_visco_hoyo_2015, title={Genotype-epigenotype interaction at the IGF2 DMR}, volume={6}, number={3}, journal={Genes}, author={Murphy, S. K. and Erginer, E. and Huang, Z. Q. and Visco, Z. and Hoyo, C.}, year={2015}, pages={777–789} }
 @article{king_darrah_money_meentemeyer_maguire_nye_michener_murtha_jirtle_murphy_et al._2015, title={Geographic clustering of elevated blood heavy metal levels in pregnant women}, volume={15}, ISSN={["1471-2458"]}, DOI={10.1186/s12889-015-2379-9}, abstractNote={Cadmium (Cd), lead (Pb), mercury (Hg), and arsenic (As) exposure is ubiquitous and has been associated with higher risk of growth restriction and cardiometabolic and neurodevelopmental disorders. However, cost-efficient strategies to identify at-risk populations and potential sources of exposure to inform mitigation efforts are limited. The objective of this study was to describe the spatial distribution and identify factors associated with Cd, Pb, Hg, and As concentrations in peripheral blood of pregnant women.Heavy metals were measured in whole peripheral blood of 310 pregnant women obtained at gestational age ~12 weeks. Prenatal residential addresses were geocoded and geospatial analysis (Getis-Ord Gi* statistics) was used to determine if elevated blood concentrations were geographically clustered. Logistic regression models were used to identify factors associated with elevated blood metal levels and cluster membership.Geospatial clusters for Cd and Pb were identified with high confidence (p-value for Gi* statistic <0.01). The Cd and Pb clusters comprised 10.5 and 9.2 % of Durham County residents, respectively. Medians and interquartile ranges of blood concentrations (μg/dL) for all participants were Cd 0.02 (0.01-0.04), Hg 0.03 (0.01-0.07), Pb 0.34 (0.16-0.83), and As 0.04 (0.04-0.05). In the Cd cluster, medians and interquartile ranges of blood concentrations (μg/dL) were Cd 0.06 (0.02-0.16), Hg 0.02 (0.00-0.05), Pb 0.54 (0.23-1.23), and As 0.05 (0.04-0.05). In the Pb cluster, medians and interquartile ranges of blood concentrations (μg/dL) were Cd 0.03 (0.02-0.15), Hg 0.01 (0.01-0.05), Pb 0.39 (0.24-0.74), and As 0.04 (0.04-0.05). Co-exposure with Pb and Cd was also clustered, the p-values for the Gi* statistic for Pb and Cd was <0.01. Cluster membership was associated with lower education levels and higher pre-pregnancy BMI.Our data support that elevated blood concentrations of Cd and Pb are spatially clustered in this urban environment compared to the surrounding areas. Spatial analysis of metals concentrations in peripheral blood or urine obtained routinely during prenatal care can be useful in surveillance of heavy metal exposure.}, number={1}, journal={BMC PUBLIC HEALTH}, publisher={Springer Science and Business Media LLC}, author={King, Katherine E. and Darrah, Thomas H. and Money, Eric and Meentemeyer, Ross and Maguire, Rachel L. and Nye, Monica D. and Michener, Lloyd and Murtha, Amy P. and Jirtle, Randy and Murphy, Susan K. and et al.}, year={2015}, month={Oct} }
 @article{vidal_skaar_maguire_dodor_musselwhite_bartlett_oneko_obure_mlay_murphy_et al._2015, title={IL-10, IL-15, IL-17, and GMCSF levels in cervical cancer tissue of Tanzanian women infected with HPV16/18 vs. non-HPV16/18 genotypes}, volume={10}, journal={Infectious Agents and Cancer}, author={Vidal, A. C. and Skaar, D. and Maguire, R. and Dodor, S. and Musselwhite, L. W. and Bartlett, J. A. and Oneko, O. and Obure, J. and Mlay, P. and Murphy, S. K. and et al.}, year={2015} }
 @article{nye_hoyo_murphy_2015, title={In vitro lead exposure changes DNA methylation and expression of IGF2 and PEG1/MEST}, volume={29}, ISSN={["1879-3177"]}, DOI={10.1016/j.tiv.2015.01.002}, abstractNote={Epigenetic processes, such as changes in DNA methylation, likely mediate the link between environmental exposures in utero and altered gene expression. Differentially methylated regions (DMRs) that regulate imprinted genes may be especially vulnerable to environmental exposures since imprinting is established and maintained largely through DNA methylation, resulting in expression from only one parental chromosome. We used the human embryonic kidney cell line, HEK-293, to investigate the effects of exposure to physiologically relevant doses of lead acetate (Pb) on the methylation status of nine imprinted gene DMRs. We assessed mean methylation after seventy-two hours of Pb exposure (0–25 μg/dL) using bisulfite pyrosequencing. The PEG1/MEST and IGF2 DMRs had maximum methylation decreases of 9.6% (20 μg/dL; p < 0.005) and 3.8% (25 μg/dL; p < 0.005), respectively. Changes at the MEG3 DMRs had a maximum decrease in methylation of 2.9% (MEG3) and 1.8% (MEG3-IG) at 5 μg/dL Pb, but were not statistically significant. The H19, NNAT, PEG3, PLAGL1, and SGCE/PEG10 DMRs showed a less than 0.5% change in methylation, across the dose range used, and were deemed non-responsive to Pb in our model. Pb exposure below reportable/actionable levels increased expression of PEG1/MEST concomitant with decreased methylation. These results suggest that Pb exposure can stably alter the regulatory capacity of multiple imprinted DMRs.}, number={3}, journal={TOXICOLOGY IN VITRO}, author={Nye, Monica D. and Hoyo, Cathrine and Murphy, Susan K.}, year={2015}, month={Apr}, pages={544–550} }
 @article{zapata_howard_frank_ross_hoyo_grant_freedland_vidal_2015, title={MP14-06 SELF-REPORTED SEXUAL FUNCTION IS ASSOCIATED WITH PROSTATE CANCER RISK}, volume={193}, ISSN={0022-5347 1527-3792}, url={http://dx.doi.org/10.1016/J.JURO.2015.02.868}, DOI={10.1016/J.JURO.2015.02.868}, abstractNote={You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History III1 Apr 2015MP14-06 SELF-REPORTED SEXUAL FUNCTION IS ASSOCIATED WITH PROSTATE CANCER RISK Daniel Zapata, Lauren E. Howard, Jennifer Frank, Simon Ross, Catherine Hoyo, Dolores Grant, Stephen J. Freedland, and Adriana C. Vidal Daniel ZapataDaniel Zapata More articles by this author , Lauren E. HowardLauren E. Howard More articles by this author , Jennifer FrankJennifer Frank More articles by this author , Simon RossSimon Ross More articles by this author , Catherine HoyoCatherine Hoyo More articles by this author , Dolores GrantDolores Grant More articles by this author , Stephen J. FreedlandStephen J. Freedland More articles by this author , and Adriana C. VidalAdriana C. Vidal More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.868AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Introduction and objectives: Erectile dysfunction and prostate cancer (PC) are prevalent conditions among older men. To date, few studies have explored the association between these two conditions. Therefore, we tested if there is an association between sexual function and the risk of PC among men undergoing prostate biopsy. METHODS We reviewed data of 448 men undergoing prostate biopsy at a Veterans Affairs Medical Center. Sexual function data were obtained from the Expanded Prostate Cancer Index Composite sexual assessment which queries ability to have an erection, reach an orgasm, quality and frequency of erections, overall sexual function and a bother index. Most questions had a score from 1–5 (1=very poor, 5=very good). Each number was mapped to a 0–100 score and scores were averaged to create an overall sexual function score ranging from 0–100. Men with a positive biopsy were divided into low- (Gleason≤6) and high-grade (Gleason ≥7) disease. Logistic regression was used to test the link between sexual function and PC risk. Multinomial logistic regression was used to test the association between sexual function and risk of low-grade vs. no cancer and risk of high-grade vs. no cancer. RESULTS 209 (47%) men had a positive biopsy; these men were less likely to be white (43% vs. 55%, p=0.01), more recently accrued (2010 vs. 2009, p=0.002), had higher PSA (6.0 vs. 5.4ng/ml, p<0.001) but lower mean sexual function score (47 vs. 54, p<0.001). There was no difference in age, BMI, pack years smoked, history of heart disease and/or diabetes. Sexual function was linked with a decreased risk of overall PC risk (OR 0.91 per 10-pt change in sexual function, p=0.004) and high grade disease (OR 0.86, p=0.001). There was no association between sexual function and low grade PC. CONCLUSIONS Among men undergoing prostate biopsy, higher sexual function was associated with a decreased risk of overall and high-grade PC. Confirmatory studies are needed. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e152-e153 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel Zapata More articles by this author Lauren E. Howard More articles by this author Jennifer Frank More articles by this author Simon Ross More articles by this author Catherine Hoyo More articles by this author Dolores Grant More articles by this author Stephen J. Freedland More articles by this author Adriana C. Vidal More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...}, number={4S}, journal={Journal of Urology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Zapata, Daniel and Howard, Lauren E. and Frank, Jennifer and Ross, Simon and Hoyo, Catherine and Grant, Dolores and Freedland, Stephen J. and Vidal, Adriana C.}, year={2015}, month={Apr} }
 @article{guerrios_howard_sourbeer_arulraja_beverly_grant_hoyo_freedland_2015, title={MP14-11 IS BMI THE BEST ADIPOSITY MEASURE FOR PROSTATE CANCER RISK?}, volume={193}, ISSN={0022-5347 1527-3792}, url={http://dx.doi.org/10.1016/J.JURO.2015.02.873}, DOI={10.1016/J.JURO.2015.02.873}, abstractNote={You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History III1 Apr 2015MP14-11 IS BMI THE BEST ADIPOSITY MEASURE FOR PROSTATE CANCER RISK? Lourdes Guerrios, Lauren Howard, Katherine Sourbeer, Evangeline Arulraja, Devon Beverly, Delores J. Grant, Catherine Hoyo, and Steve Freedland Lourdes GuerriosLourdes Guerrios More articles by this author , Lauren HowardLauren Howard More articles by this author , Katherine SourbeerKatherine Sourbeer More articles by this author , Evangeline ArulrajaEvangeline Arulraja More articles by this author , Devon BeverlyDevon Beverly More articles by this author , Delores J. GrantDelores J. Grant More articles by this author , Catherine HoyoCatherine Hoyo More articles by this author , and Steve FreedlandSteve Freedland More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.873AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The association between body mass index (BMI) and prostate cancer (PC) risk is mixed. Some have speculated that this relates to the fact that BMI is only a moderate measure of adiposity and that perhaps better measures (total percent body fat) or that central adiposity (waist circumference) may better correlate with PC risk. We tested multiple measures of adiposity and PC risk using prospectively collected and measured data from men undergoing prostate biopsies in a Veterans Affairs hospital. We hypothesized that on the aggregate level, BMI, total percent body fat and waist circumference would be highly correlated and that all would be associated with aggressive PC, but not overall incidence. METHODS We used data from a case-control study among veterans between 2007 and 2012 undergoing prostate biopsy at the Durham Veterans Affairs. The sample consisted of 323 (46%) with biopsy-positive PC (cases) and 375 (54%) biopsy negative (controls). We abstracted Gleason score and race from the records. Weight, height, and waist circumference were measured by trained personnel. Body fat was measured using bio-impedance. We used logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs) to test the association between adiposity measures and PC risk. Multinomial logistic regression was used to examined high-grade PC (Gleason 7–10) vs. low-grade (2–6) vs. no-PC. RESULTS BMI was strongly related to percent body fat (Spearman, r=0.81) and waist circumference (r=0.87). Men with higher BMI had significantly higher TRUS prostate volumes, percent body fat, and waist circumference. In both adjusted and unadjusted logistic regression analyses, all three adiposity measures were unrelated to total PC risk (all p>=0.14). However, when stratified by Gleason score, all adiposity measures were associated with a significantly increased risk of high-grade disease (all p<0.009) but none were related to low-grade PC (all p>=0.35). CONCLUSIONS BMI, body fat and waist circumference are all highly correlated with each other and all were significantly associated with aggressive PC, but not overall PC risk. Despite individual differences in these measures, this study supports the continued use of BMI in epidemiological studies of obesity and PC. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e155 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lourdes Guerrios More articles by this author Lauren Howard More articles by this author Katherine Sourbeer More articles by this author Evangeline Arulraja More articles by this author Devon Beverly More articles by this author Delores J. Grant More articles by this author Catherine Hoyo More articles by this author Steve Freedland More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...}, number={4S}, journal={Journal of Urology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Guerrios, Lourdes and Howard, Lauren and Sourbeer, Katherine and Arulraja, Evangeline and Beverly, Devon and Grant, Delores J. and Hoyo, Catherine and Freedland, Steve}, year={2015}, month={Apr} }
 @article{vidal_semenova_darrah_vengosh_huang_king_nye_fry_skaar_maguire_et al._2015, title={Maternal cadmium, iron and zinc levels, DNA methylation and birth weight}, volume={16}, journal={BMC Pharmacology & Toxicology}, author={Vidal, A. C. and Semenova, V. and Darrah, T. and Vengosh, A. and Huang, Z. Q. and King, K. and Nye, M. D. and Fry, R. and Skaar, D. and Maguire, R. and et al.}, year={2015} }
 @article{soubry_hoyo_jirtle_murphy_2014, title={A paternal environmental legacy: Evidence for epigenetic inheritance through the male germ line}, volume={36}, ISSN={0265-9247}, url={http://dx.doi.org/10.1002/BIES.201300113}, DOI={10.1002/BIES.201300113}, abstractNote={Literature on maternal exposures and the risk of epigenetic changes or diseases in the offspring is growing. Paternal contributions are often not considered. However, some animal and epidemiologic studies on various contaminants, nutrition, and lifestyle-related conditions suggest a paternal influence on the offspring's future health. The phenotypic outcomes may have been attributed to DNA damage or mutations, but increasing evidence shows that the inheritance of environmentally induced functional changes of the genome, and related disorders, are (also) driven by epigenetic components. In this essay we suggest the existence of epigenetic windows of susceptibility to environmental insults during sperm development. Changes in DNA methylation, histone modification, and non-coding RNAs are viable mechanistic candidates for a non-genetic transfer of paternal environmental information, from maturing germ cell to zygote. Inclusion of paternal factors in future research will ultimately improve the understanding of transgenerational epigenetic plasticity and health-related effects in future generations.}, number={4}, journal={BioEssays}, publisher={Wiley}, author={Soubry, Adelheid and Hoyo, Cathrine and Jirtle, Randy L. and Murphy, Susan K.}, year={2014}, month={Jan}, pages={359–371} }
 @article{vidal_williams_allott_howard_grant_mcphail_sourbeer_hwa_boffetta_hoyo_et al._2014, title={Carbohydrate intake, glycemic index and prostate cancer risk}, volume={75}, ISSN={0270-4137}, url={http://dx.doi.org/10.1002/PROS.22929}, DOI={10.1002/PROS.22929}, abstractNote={Reported associations between dietary carbohydrate and prostate cancer (PC) risk are poorly characterized by race.We analyzed the association between carbohydrate intake, glycemic index (GI), and PC risk in a study of white (N = 262) and black (N = 168) veterans at the Durham VA Hospital. Cases were 156 men with biopsy-confirmed PC and controls (N = 274) had a PSA test but were not recommended for biopsy. Diet was assessed before biopsy with a self-administered food frequency questionnaire. Logistic regression models were used to estimate PC risk.In multivariable analyzes, higher carbohydrate intake, measured as percent of energy from carbohydrates, was associated with reduced PC risk (3rd vs. 1st tertile, OR = 0.41, 95% CI 0.21-0.81, P = 0.010), though this only reached significance in white men (p-trend = 0.029). GI was unrelated to PC risk among all men, but suggestively linked with reduced PC risk in white men (p-trend = 0.066) and increased PC risk in black men (p-trend = 0.172), however, the associations were not significant. Fiber intake was not associated with PC risk (all p-trends > 0.55). Higher carbohydrate intake was associated with reduced risk of high-grade (p-trend = 0.016), but not low-grade PC (p-trend = 0.593).Higher carbohydrate intake may be associated with reduced risk of overall and high-grade PC. Future larger studies are needed to confirm these findings.}, number={4}, journal={The Prostate}, publisher={Wiley}, author={Vidal, Adriana C. and Williams, Christina D. and Allott, Emma H. and Howard, Lauren E. and Grant, Delores J. and McPhail, Megan and Sourbeer, Katharine N. and Hwa, Lin Pao and Boffetta, Paolo and Hoyo, Cathrine and et al.}, year={2014}, month={Nov}, pages={430–439} }
 @article{soubry_verbeke_hoyo_2014, title={Do early paternal exposures to lifestyle factors such as smoking increase the risk of chronic diseases in the offspring?}, volume={22}, ISSN={1018-4813 1476-5438}, url={http://dx.doi.org/10.1038/EJHG.2014.206}, DOI={10.1038/EJHG.2014.206}, abstractNote={Do early paternal exposures to lifestyle factors such as smoking increase the risk of chronic diseases in the offspring?}, number={12}, journal={European Journal of Human Genetics}, publisher={Springer Science and Business Media LLC}, author={Soubry, Adelheid and Verbeke, Geert and Hoyo, Cathrine}, year={2014}, month={Oct}, pages={1341–1342} }
 @article{hoyo_daltveit_iversen_benjamin-neelon_fuemmeler_schildkraut_murtha_overcash_vidal_wang_et al._2014, title={Erythrocyte folate concentrations, CpG methylation at genomically imprinted domains, and birth weight in a multiethnic newborn cohort}, volume={9}, ISSN={["1559-2308"]}, DOI={10.4161/epi.29332}, abstractNote={Epigenetic mechanisms are proposed to link maternal concentrations of methyl group donor nutrients with the risk of low birth weight. However, empirical data are lacking. We have examined the association between maternal folate and birth weight and assessed the mediating role of DNA methylation at nine differentially methylated regions (DMRs) of genomically imprinted genes in these associations. Compared with newborns of women with folate levels in the lowest quartile, birth weight was higher in newborns of mothers in the second (β = 143.2, se = 63.2, P = 0.02), third (β = 117.3, se = 64.0, P = 0.07), and fourth (β = 133.9, se = 65.2, P = 0.04) quartiles, consistent with a threshold effect. This pattern of association did not vary by race/ethnicity but was more apparent in newborns of non-obese women. DNA methylation at the PLAGL1, SGCE, DLK1/MEG3 and IGF2/H19 DMRs was associated with maternal folate levels and also birth weight, suggestive of threshold effects. MEG3 DMR methylation mediated the association between maternal folate levels and birth weight (P =0.06). While the small sample size and partial scope of examined DMRs limit our conclusions, our data suggest that, with respect to birth weight, no additional benefits may be derived from increased maternal folate concentrations, especially in non-obese women. These data also support epigenetic plasticity as a key mechanistic response to folate availability during early fetal development.}, number={8}, journal={EPIGENETICS}, author={Hoyo, Cathrine and Daltveit, Anne Kjersti and Iversen, Edwin and Benjamin-Neelon, Sara E. and Fuemmeler, Bernard and Schildkraut, Joellen and Murtha, Amy P. and Overcash, Francine and Vidal, Adriana C. and Wang, Frances and et al.}, year={2014}, month={Aug}, pages={1120–1130} }
 @article{vidal_smith_valea_bentley_gradison_yarnall_ford_overcash_grant_murphy_et al._2014, title={HPV genotypes and cervical intraepithelial neoplasia in a multiethnic cohort in the southeastern USA}, volume={25}, ISSN={["1573-7225"]}, DOI={10.1007/s10552-014-0406-2}, abstractNote={For poorly understood reasons, invasive cervical cancer (ICC) incidence and mortality rates are higher in women of African descent. Oncogenic human papillomavirus (HPV) genotypes distribution may vary between European American (EA) and African-American (AA) women and may contribute to differences in ICC incidence. The current study aimed at disentangling differences in HPV distribution among AA and EA women.Five-hundred and seventy-two women were enrolled at the time of colposcopic evaluation following an abnormal liquid-based cytology screen. HPV infections were detected using HPV linear array, and chi-squared tests and linear regression models were used to compare HPV genotypes across racial/ethnic groups by CIN status.Of the 572 participants, 494 (86 %) had detectable HPV; 245 (43 %) had no CIN lesion, 239 (42 %) had CIN1, and 88 (15 %) had CIN2/3. Seventy-three percent of all women were infected with multiple HPV genotypes. After adjusting for race, age, parity, income, oral contraception use, and current smoking, AAs were two times less likely to harbor HPV 16/18 (OR 0.48, 95 % CI 0.21-0.94, p = 0.03) when all women were considered. This association remained unchanged when only women with CIN2/3 lesions were examined (OR 0.22, 95 % CI 0.05-0.95, p = 0.04). The most frequent high-risk HPV genotypes detected among EAs were 16, 18, 56, 39, and 66, while HPV genotypes 33, 35, 45, 58, and 68 were the most frequent ones detected in AAs.Our data suggest that while HPV 16/18 are the most common genotypes among EA women with CIN, AAs may harbor different genotypes.}, number={8}, journal={CANCER CAUSES & CONTROL}, author={Vidal, Adriana C. and Smith, Jennifer S. and Valea, Fidel and Bentley, Rex and Gradison, Maggie and Yarnall, Kimberly S. H. and Ford, Anne and Overcash, Francine and Grant, Kathy and Murphy, Susan K. and et al.}, year={2014}, month={Aug}, pages={1055–1062} }
 @article{vidal_williams_allott_howard_grant_mcphail_sourbeer_boffetta_hoyo_freedland_2014, title={PD31-11 CARBOHYDRATE INTAKE, GLYCEMIC INDEX AND PROSTATE CANCER RISK}, volume={191}, ISSN={0022-5347 1527-3792}, url={http://dx.doi.org/10.1016/J.JURO.2014.02.2270}, DOI={10.1016/J.JURO.2014.02.2270}, abstractNote={You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History I1 Apr 2014PD31-11 CARBOHYDRATE INTAKE, GLYCEMIC INDEX AND PROSTATE CANCER RISK Adriana C. Vidal, Christina Williams, Emma H. Allott, Lauren E. Howard, Delores J. Grant, Megan McPhail, Katharine N. Sourbeer, Paolo Boffetta, Cathrine Hoyo, and Stephen J. Freedland Adriana C. VidalAdriana C. Vidal More articles by this author , Christina WilliamsChristina Williams More articles by this author , Emma H. AllottEmma H. Allott More articles by this author , Lauren E. HowardLauren E. Howard More articles by this author , Delores J. GrantDelores J. Grant More articles by this author , Megan McPhailMegan McPhail More articles by this author , Katharine N. SourbeerKatharine N. Sourbeer More articles by this author , Paolo BoffettaPaolo Boffetta More articles by this author , Cathrine HoyoCathrine Hoyo More articles by this author , and Stephen J. FreedlandStephen J. Freedland More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2270AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Reported associations between dietary carbohydrate and prostate cancer (PC) risk are inconsistent and poorly characterized by race. We examined the associations between dietary carbohydrate intake, glycemic index (GI), and PC risk in blacks and whites. METHODS We analyzed data from an ongoing case-control study of white (N=262) and black (N=168) veterans at the Durham VA Hospital. Cases were 156 men with biopsy-confirmed PC. Controls were men who had undergone PSA testing but were not recommended for further evaluation. Demographic and lifestyle risk data were collected using self-administered questionnaires prior to diagnosis. Diet information was obtained using the Harvard food frequency questionnaire. Logistic regression models were used to estimate PC risk and results were adjusted for age, race, body mass index and caloric intake. RESULTS Among controls, median carbohydrate intake was 224 gms/day, which amounted to 49% (IQR 43-55%) of calories from carbohydrates. Higher total carbohydrate intake was associated with reduced PC risk (3rd tertile vs. 1st tertile, OR=0.29, 95%CI 0.11-0.72, p-trend=0.007). Though associations were similar in black and white men, this only reached significance in black men (p-trend=0.007). When carbohydrate intake was measured as percent of energy from carbohydrates, higher intake was associated with reduced PC risk (3rd tertile vs. 1st tertile, OR=0.57, 95%CI 0.34-0.96, p=0.033). Again, results were similar in both races, though this only reached significance in black men (p-trend=0.025). Similarly, higher fiber intake (p-trend=0.047) was associated with lower risk of PC, with results similar in black and white men. In contrast, GI was unrelated to PC risk among all men with a suggestion that higher GI may be linked with increased PC risk in black men (p-trend=0.06). When stratified by grade, associations for all dietary factors examined were similar for both low- and high-grade disease. CONCLUSIONS Among men consuming a Western diet, our findings suggest higher carbohydrate intake and thereby lower intake of other macronutrients (i.e. protein and fat) may be associated with reduced risk of overall PC and both low- and high-grade PC. However, when examining the GI of the diet, there was no association, although there was a suggestion that high GI foods may increase PC risk in black men. While larger studies are needed to confirm our findings, these data suggest that among men consuming a Western diet, those eating more complex carbohydrates (i.e. fiber, whole grains) but not refined carbohydrates may have lower PC risk. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e835 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Adriana C. Vidal More articles by this author Christina Williams More articles by this author Emma H. Allott More articles by this author Lauren E. Howard More articles by this author Delores J. Grant More articles by this author Megan McPhail More articles by this author Katharine N. Sourbeer More articles by this author Paolo Boffetta More articles by this author Cathrine Hoyo More articles by this author Stephen J. Freedland More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...}, number={4S}, journal={Journal of Urology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Vidal, Adriana C. and Williams, Christina and Allott, Emma H. and Howard, Lauren E. and Grant, Delores J. and McPhail, Megan and Sourbeer, Katharine N. and Boffetta, Paolo and Hoyo, Cathrine and Freedland, Stephen J.}, year={2014}, month={Apr} }
 @article{gaines_turner_moorman_freedland_keto_mcphail_grant_vidal_hoyo_2014, title={The association between race and prostate cancer risk on initial biopsy in an equal access, multiethnic cohort}, volume={25}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/S10552-014-0402-6}, DOI={10.1007/S10552-014-0402-6}, abstractNote={Population-based studies have established a link between race and prostate cancer (PC) risk, but whether race predicts PC after adjusting for clinical characteristics is unclear. We investigated the association between race and risk of low- and high-grade PC in men undergoing initial prostate biopsy in an equal access medical center.We conducted a retrospective record review of 887 men (48.6 % black, 51.4 % white) from the Durham Veterans Affairs Medical Center who underwent initial prostate biopsy between 2001 and 2009. Multivariable logistic regression analysis of race and biopsy outcome was conducted adjusting for age, body mass index, number of cores taken, prostate-specific antigen (PSA), and digital rectal examination findings. Multinomial logistic regression was used to test the association between black race and PC grade (Gleason <7 vs. ≥7).Black men were younger at biopsy (61 vs. 65 years, p < 0.001) and had a higher pre-biopsy PSA (6.6 vs. 5.8 ng/ml, p = 0.001). A total of 499 men had PC on biopsy (245 low grade; 254 high grade). In multivariable analyses, black race was significantly predictive of PC overall [odds ratio 1.50, p = 0.006] and high-grade PC [relative risk ratio (RRR) 1.84, p = 0.001], but was not significantly associated with low-grade PC (RRR 1.29, p = 0.139).In an equal access healthcare facility, black race was associated with greater risk of PC detection on initial biopsy and of high-grade PC after adjusting for clinical characteristics. Additional investigation of mechanisms linking black race and PC risk and PC aggressiveness is needed.}, number={8}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Gaines, Alexis R. and Turner, Elizabeth L. and Moorman, Patricia G. and Freedland, Stephen J. and Keto, Christopher J. and McPhail, Megan E. and Grant, Delores J. and Vidal, Adriana C. and Hoyo, Cathrine}, year={2014}, month={May}, pages={1029–1035} }
 @article{liu_hoyo_murphy_overcash_thompson_brown_murtha_2013, title={75: DNA methylation at imprinted regulatory regions in preterm birth and infection}, volume={208}, ISSN={0002-9378}, url={http://dx.doi.org/10.1016/j.ajog.2012.10.240}, DOI={10.1016/j.ajog.2012.10.240}, number={1}, journal={American Journal of Obstetrics and Gynecology}, publisher={Elsevier BV}, author={Liu, Ying and Hoyo, Cathrine and Murphy, Susan and Overcash, Francine and Thompson, Jennifer and Brown, Haywood and Murtha, Amy}, year={2013}, month={Jan}, pages={S45} }
 @article{thomas_antonelli_banez_hoyo_grant_demark-wahnefried_platz_gerber_shuler_eyoh_et al._2013, title={Androgenetic alopecia at various ages and prostate cancer risk in an equal-access multiethnic case–control series of veterans}, volume={24}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/S10552-013-0182-4}, DOI={10.1007/S10552-013-0182-4}, abstractNote={Epidemiological data are conflicting regarding the association between androgenetic alopecia (AA) and prostate cancer (CaP). We examined the relationship between these two conditions.We performed a case-control study at a Veterans Affairs Hospital among 708 men: 312 healthy controls, 167 men with CaP, and 229 men without CaP on prostate biopsy. Participants were asked to self-describe hair patterns at ages 30 and 40 and at study enrollment. We tested the association between hair pattern (overall, vertex, or frontal) and CaP status using logistic regression analysis adjusting for multiple clinical features. Disease grade was similarly examined as a secondary outcome.Relative to healthy controls, younger age of AA onset was significantly associated with increased CaP risk (p = 0.008). Similar patterns were noted for frontal (p = 0.005) and not vertex balding (p = 0.22). When compared with biopsy-negative men, a similar pattern was seen with younger age of AA onset having higher risk of CaP, though this was not significant (p = 0.07). A suggestion for younger age of AA onset for frontal (p = 0.07) being associated with CaP versus biopsy-negative men was also observed. Overall balding (yes/no) was associated with greater than twofold increase in high-grade disease (p = 0.02).Men reporting earlier AA onset were at increased CaP risk and suggestively had more aggressive disease. Contrary to other studies, frontal balding was the predominant pattern associated with elevated CaP risk. Further study is required to confirm these findings in a larger sample and to better understand the role of AA, androgens, and CaP biology.}, number={5}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Thomas, Jean-Alfred and Antonelli, Jodi A. and Banez, Lionel L. and Hoyo, Catherine and Grant, Delores and Demark-Wahnefried, Wendy and Platz, Elizabeth A. and Gerber, Leah and Shuler, Kathryn and Eyoh, Enwono and et al.}, year={2013}, month={Mar}, pages={1045–1052} }
 @article{singh_jones_antonelli_gerber_calloway_shuler_freedland_grant_hoyo_bañez_2013, title={Association between exercise and primary incidence of prostate cancer}, volume={119}, ISSN={0008-543X}, url={http://dx.doi.org/10.1002/CNCR.27791}, DOI={10.1002/CNCR.27791}, abstractNote={BACKGROUND: Exercise is a modifiable lifestyle risk factor associated with prostate cancer risk reduction. However, whether this association is different as a function of race is unclear. In the current study, the authors attempted to characterize the link between exercise and prostate cancer (CaP) in white and black American men. METHODS: Using a prospective design, 307 men (164 of whom were white and 143 of whom were black) who were undergoing prostate biopsy completed a self-reported survey that assessed exercise behavior (metabolic equivalent [MET] hours per week). Crude and adjusted logistic regression analyses were used to estimate the risk of prostate cancer controlling for age, body mass index, digital rectal examination findings, previous biopsy, Charlson comorbidity score, and family history of CaP stratified by self-reported race. RESULTS: There was no significant difference noted with regard to the amount of exercise between racial groups (P = .12). Higher amounts of MET hours per week were associated with a decreased risk of CaP for white men in both crude (P = .02) and adjusted (P = .04) regression models. Among whites, men who exercised ≥ 9 MET hours per week were less likely to have a positive biopsy result compared with men exercising < 9 MET hours per week (odds ratio, 0.47; 95% confidence interval, 0.22-0.99 [P = .047]). There was no association noted between MET hours per week and risk of CaP among black men in both crude (P = .79) and adjusted (P = .76) regression models. CONCLUSIONS: In a prospective cohort of men undergoing biopsy, increased exercise, measured as MET hours per week, was found to be associated with CaP risk reduction among white but not black men. Investigating race-specific mechanisms by which exercise modifies CaP risk and why these mechanisms disfavor black men in particular are warranted. Cancer 2013. © 2013 American Cancer Society.}, number={7}, journal={Cancer}, publisher={Wiley}, author={Singh, Abhay A. and Jones, Lee W. and Antonelli, Jodi A. and Gerber, Leah and Calloway, Elizabeth E. and Shuler, Kathleen H. and Freedland, Stephen J. and Grant, Delores J. and Hoyo, Cathrine and Bañez, Lionel L.}, year={2013}, month={Feb}, pages={1338–1343} }
 @article{vidal_murphy_murtha_schildkraut_soubry_huang_neelon_fuemmeler_iversen_wang_et al._2013, title={Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring}, volume={37}, ISSN={0307-0565 1476-5497}, url={http://dx.doi.org/10.1038/IJO.2013.47}, DOI={10.1038/IJO.2013.47}, abstractNote={Low birth weight (LBW) has been associated with common adult-onset chronic diseases, including obesity, cardiovascular disease, type II diabetes and some cancers. The etiology of LBW is multi-factorial. However, recent evidence suggests exposure to antibiotics may also increase the risk of LBW. The mechanisms underlying this association are unknown, although epigenetic mechanisms are hypothesized. In this study, we evaluated the association between maternal antibiotic use and LBW and examined the potential role of altered DNA methylation that controls growth regulatory imprinted genes in these associations. Between 2009–2011, 397 pregnant women were enrolled and followed until delivery. Prenatal antibiotic use was ascertained through maternal self-report. Imprinted genes methylation levels were measured at differentially methylated regions (DMRs) using bisulfite pyrosequencing. Generalized linear models were used to examine associations among antibiotic use, birth weight and DMR methylation fractions. After adjusting for infant gender, race/ethnicity, maternal body mass index, delivery route, gestational weight gain, gestational age at delivery, folic acid intake, physical activity, maternal smoking and parity, antibiotic use during pregnancy was associated with 138 g lower birth weight compared with non-antibiotic use (β-coefficient=−132.99, s.e.=50.70, P=0.008). These associations were strongest in newborns of women who reported antibiotic use other than penicillins (β-coefficient=−135.57, s.e.=57.38, P=0.02). Methylation at five DMRs, IGF2 (P=0.05), H19 (P=0.15), PLAGL1 (P=0.01), MEG3 (P=0.006) and PEG3 (P=0.08), was associated with maternal antibiotic use; among these, only methylation at the PLAGL1 DMR was also associated with birth weight. We report an inverse association between in utero exposure to antibiotics and lower infant birth weight and provide the first empirical evidence supporting imprinted gene plasticity in these associations.}, number={7}, journal={International Journal of Obesity}, publisher={Springer Science and Business Media LLC}, author={Vidal, A C and Murphy, S K and Murtha, A P and Schildkraut, J M and Soubry, A and Huang, Z and Neelon, S E B and Fuemmeler, B and Iversen, E and Wang, F and et al.}, year={2013}, month={Mar}, pages={907–913} }
 @article{liu_hoyo_murphy_huang_overcash_thompson_brown_murtha_2013, title={DNA methylation at imprint regulatory regions in preterm birth and infection}, volume={208}, ISSN={0002-9378}, url={http://dx.doi.org/10.1016/J.AJOG.2013.02.006}, DOI={10.1016/J.AJOG.2013.02.006}, abstractNote={To aid in understanding long-term health consequences of intrauterine infections in preterm birth, we evaluated DNA methylation at 9 differentially methylated regions that regulate imprinted genes by type of preterm birth (spontaneous preterm labor, preterm premature rupture of membranes, or medically indicated [fetal growth restriction and preeclampsia]) and infection status (chorioamnionitis or funisitis).Data on type of preterm birth and infection status were abstracted from medical records and standardized pathology reports in 73 preterm infants enrolled in the Newborn Epigenetics STudy, a prospective cohort study of mother-infant dyads in Durham, NC. Cord blood was collected at birth, and infant DNA methylation levels at the H19, IGF2, MEG3, MEST, SGCE/PEG10, PEG3, NNAT, and PLAGL1 differentially methylated regions were measured using bisulfite pyrosequencing. One-way analyses of variance and logistic regression models were used to compare DNA methylation levels by type of preterm birth and infection status.DNA methylation levels did not differ at any of the regions (P > .20) between infants born via spontaneous preterm labor (average n = 29), preterm premature rupture of membranes (average n = 17), or medically indicated preterm birth (average n = 40). Levels were significantly increased at PLAGL1 in infants with chorioamnionitis (n = 10, 64.4%) compared with infants without chorioamnionitis (n = 63, 57.9%), P < .01. DNA methylation levels were also increased at PLAGL1 for infants with funisitis (n = 7, 63.3%) compared with infants without funisitis (n = 66, 58.3%), P < .05.Dysregulation of PLAGL1 has been associated with abnormal development and cancer. Early-life exposures, including infection/inflammation, may affect epigenetic changes that increase susceptibility to later chronic disease.}, number={5}, journal={American Journal of Obstetrics and Gynecology}, publisher={Elsevier BV}, author={Liu, Ying and Hoyo, Cathrine and Murphy, Susan and Huang, Zhiqing and Overcash, Francine and Thompson, Jennifer and Brown, Haywood and Murtha, Amy P.}, year={2013}, month={May}, pages={395.e1–395.e7} }
 @article{fish_moorman_wordlaw-stintson_vidal_smith_hoyo_2013, title={Factors Associated With Adherence to Follow-up Colposcopy}, volume={44}, ISSN={1932-5037 2168-3751}, url={http://dx.doi.org/10.1080/19325037.2013.838881}, DOI={10.1080/19325037.2013.838881}, abstractNote={Understanding the gaps in knowledge about human papilloma virus (HPV) infection, transmission, and health consequences and factors associated with the knowledge gap is an essential first step for the development of interventions to improve adherence to follow-up among women with abnormal Pap smears.To examine the relationship between knowledge about HPV and adherence to scheduled colposcopic evaluation and variables related to lack of knowledge among women with abnormal Pap tests.Telephone surveys were conducted with women who attended their scheduled appointments (adherers) and women who did not attend their appointments (nonadherers).The multivariable analyses indicate that lower HPV knowledge was independently associated with nonadherence to follow-up, controlling for race and education level. Factors related to lower knowledge scores included non-white race, lower education, and lack of health insurance at the time of the scheduled appointment.Lack of knowledge of HPV was related to nonadherence among women scheduled for colposcopic evaluation.Health education interventions that deliver complex information about HPV and cervical cancer should be in a format that is accessible and understandable to the women who are most at risk of being nonadherent.}, number={6}, journal={American Journal of Health Education}, publisher={Informa UK Limited}, author={Fish, Laura J. and Moorman, Patricia G. and Wordlaw-Stintson, Lashawn and Vidal, Adriana and Smith, Jennifer S. and Hoyo, Cathrine}, year={2013}, month={Nov}, pages={293–298} }
 @article{soubry_murphy_wang_huang_vidal_fuemmeler_kurtzberg_murtha_jirtle_schildkraut_et al._2013, title={Newborns of obese parents have altered DNA methylation patterns at imprinted genes}, volume={39}, ISSN={0307-0565 1476-5497}, url={http://dx.doi.org/10.1038/IJO.2013.193}, DOI={10.1038/IJO.2013.193}, abstractNote={Several epidemiologic studies have demonstrated associations between periconceptional environmental exposures and health status of the offspring in later life. Although these environmentally related effects have been attributed to epigenetic changes, such as DNA methylation shifts at imprinted genes, little is known about the potential effects of maternal and paternal preconceptional overnutrition or obesity.We examined parental preconceptional obesity in relation to DNA methylation profiles at multiple human imprinted genes important in normal growth and development, such as: maternally expressed gene 3 (MEG3), mesoderm-specific transcript (MEST), paternally expressed gene 3 (PEG3), pleiomorphic adenoma gene-like 1 (PLAGL1), epsilon sarcoglycan and paternally expressed gene 10 (SGCE/PEG10) and neuronatin (NNAT).We measured methylation percentages at the differentially methylated regions (DMRs) by bisulfite pyrosequencing in DNA extracted from umbilical cord blood leukocytes of 92 newborns. Preconceptional obesity, defined as BMI ⩾30 kg m(-2), was ascertained through standardized questionnaires.After adjusting for potential confounders and cluster effects, paternal obesity was significantly associated with lower methylation levels at the MEST (β=-2.57; s.e.=0.95; P=0.008), PEG3 (β=-1.71; s.e.=0.61; P=0.005) and NNAT (β=-3.59; s.e.=1.76; P=0.04) DMRs. Changes related to maternal obesity detected at other loci were as follows: β-coefficient was +2.58 (s.e.=1.00; P=0.01) at the PLAGL1 DMR and -3.42 (s.e.=1.69; P=0.04) at the MEG3 DMR.We found altered methylation outcomes at multiple imprint regulatory regions in children born to obese parents, compared with children born to non-obese parents. In spite of the small sample size, our data suggest a preconceptional influence of parental life-style or overnutrition on the (re)programming of imprint marks during gametogenesis and early development. More specifically, the significant and independent association between paternal obesity and the offspring's methylation status suggests the susceptibility of the developing sperm for environmental insults. The acquired imprint instability may be carried onto the next generation and increase the risk for chronic diseases in adulthood.}, number={4}, journal={International Journal of Obesity}, publisher={Springer Science and Business Media LLC}, author={Soubry, A and Murphy, S K and Wang, F and Huang, Z and Vidal, A C and Fuemmeler, B F and Kurtzberg, J and Murtha, A and Jirtle, R L and Schildkraut, J M and et al.}, year={2013}, month={Oct}, pages={650–657} }
 @article{vidal_henry_murphy_oneko_nye_bartlett_overcash_huang_wang_mlay_et al._2013, title={PEG1/MEST and IGF2 DNA methylation in CIN and in cervical cancer}, volume={16}, ISSN={1699-048X 1699-3055}, url={http://dx.doi.org/10.1007/S12094-013-1067-4}, DOI={10.1007/S12094-013-1067-4}, abstractNote={Although most invasive cervical cancer (ICC) harbor <20 human papillomavirus (HPV) genotypes, use of HPV screening to predict ICC from HPV has low specificity, resulting in multiple and costly follow-up visits and overtreatment. We examined DNA methylation at regulatory regions of imprinted genes in relation to ICC and its precursor lesions to determine if methylation profiles are associated with progression of HPV-positive lesions to ICC.We enrolled 148 controls, 38 CIN and 48 ICC cases at Kilimanjaro Christian Medical Centre from 2008 to 2009. HPV was genotyped by linear array and HIV-1 serostatus was tested by two rapid HIV tests. DNA methylation was measured by bisulfite pyrosequencing at regions regulating eight imprinted domains. Logistic regression models were used to estimate odd ratios.After adjusting for age, HPV infection, parity, hormonal contraceptive use, and HIV-1 serostatus, a 10 % decrease in methylation levels at an intragenic region of IGF2 was associated with higher risk of ICC (OR 2.00, 95 % CI 1.14-3.44) and cervical intraepithelial neoplasia (CIN) (OR 1.51, 95 % CI 1.00-2.50). Methylation levels at the H19 DMR and PEG1/MEST were also associated with ICC risk (OR 1.51, 95 % CI 0.90-2.53, and OR 1.44, 95 % CI 0.90-2.35, respectively). Restricting analyses to women >30 years further strengthened these associations.While the small sample size limits inference, these findings show that altered DNA methylation at imprinted domains including IGF2/H19 and PEG1/MEST may mediate the association between HPV and ICC risk.}, number={3}, journal={Clinical and Translational Oncology}, publisher={Springer Science and Business Media LLC}, author={Vidal, A. C. and Henry, N. M. and Murphy, S. K. and Oneko, O. and Nye, M. and Bartlett, J. A. and Overcash, F. and Huang, Z. and Wang, F. and Mlay, P. and et al.}, year={2013}, month={Jun}, pages={266–272} }
 @article{grant_hoyo_akushevich_iversen_whitaker_marks_berchuck_schildkraut_2013, title={Vitamin D receptor (VDR) polymorphisms and risk of ovarian cancer in Caucasian and African American women}, volume={129}, ISSN={0090-8258}, url={http://dx.doi.org/10.1016/J.YGYNO.2012.12.027}, DOI={10.1016/J.YGYNO.2012.12.027}, abstractNote={Polymorphisms in the vitamin D receptor (VDR) gene have been shown in some studies to be associated with the risk of epithelial ovarian cancer (EOC) in Caucasian women. There are no published reports among African Americans.Case-control data from the North Carolina Ovarian Cancer Study were analyzed using logistic regression to determine the association between seven VDR polymorphisms and EOC in both Caucasians (513 cases, 532 controls) and African Americans (74 cases, 79 controls). In a larger sample of African-Americans (125 cases, 155 controls), we assessed associations between six SNPs in proximity of rs7975232.African American women who carried at least one minor allele of rs7975232 were at higher risk for invasive EOC controlling for age and admixture with an odds ratio (OR) for association under the log-additive model of 2.08 (95% confidence interval (CI)=1.19, 3.63, p=0.010). No association was observed between any of the VDR variants and EOC among Caucasians. A larger sample of African Americans revealed a nearly two-fold increased risk of invasive EOC associated with rs7305032, a SNP in proximity to rs7975232 (R(2)=0.369) with a log-additive OR of 1.87 (95% CI=1.20, 2.93, p=0.006).This is the first report showing VDR variants associated with ovarian cancer risk in African American women. A larger study of African American women is needed to confirm these findings. These results imply that vitamin D exposure is a possible modifiable risk factor of ovarian cancer among African Americans.}, number={1}, journal={Gynecologic Oncology}, publisher={Elsevier BV}, author={Grant, Delores J. and Hoyo, Cathrine and Akushevich, Lucy and Iversen, Edwin S. and Whitaker, Regina and Marks, Jeffrey and Berchuck, Andrew and Schildkraut, Joellen M.}, year={2013}, month={Apr}, pages={173–178} }
 @article{thomas_antonelli_bañez_gerber_hoyo_grant_demark-wahnefried_platz_calloway_eyoh_et al._2012, title={341 ANDROGENETIC ALOPECIA AT VARIOUS AGES AND PROSTATE CANCER RISK IN AN EQUAL ACCESS MULTIETHNIC CASE CONTROL SERIES OF VETERANS}, volume={187}, ISSN={0022-5347 1527-3792}, url={http://dx.doi.org/10.1016/j.juro.2012.02.402}, DOI={10.1016/j.juro.2012.02.402}, abstractNote={You have accessJournal of UrologyProstate Cancer: Epidemiology and Natural History II1 Apr 2012341 ANDROGENETIC ALOPECIA AT VARIOUS AGES AND PROSTATE CANCER RISK IN AN EQUAL ACCESS MULTIETHNIC CASE CONTROL SERIES OF VETERANS Jean-Alfred Thomas, Jodi A. Antonelli, Lionel L. Bañez, Leah Gerber, Cathrine Hoyo, Delores Grant, Wendy Demark-Wahnefried, Elizabeth Platz, Elizabeth Calloway, Enwono Eyoh, Kathleen Shuler, and Stephen J. Freedland Jean-Alfred ThomasJean-Alfred Thomas Durham, NC More articles by this author , Jodi A. AntonelliJodi A. Antonelli Durham, NC More articles by this author , Lionel L. BañezLionel L. Bañez Durham, NC More articles by this author , Leah GerberLeah Gerber Durham, NC More articles by this author , Cathrine HoyoCathrine Hoyo Durham, NC More articles by this author , Delores GrantDelores Grant Durham, NC More articles by this author , Wendy Demark-WahnefriedWendy Demark-Wahnefried Birmingham, AL More articles by this author , Elizabeth PlatzElizabeth Platz Balitmore, MD More articles by this author , Elizabeth CallowayElizabeth Calloway Durham, NC More articles by this author , Enwono EyohEnwono Eyoh Durham, NC More articles by this author , Kathleen ShulerKathleen Shuler Durham, NC More articles by this author , and Stephen J. FreedlandStephen J. Freedland Durham, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.402AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Epidemiological data are conflicting regarding the association between androgenetic alopecia (AA) and prostate cancer (CaP). We examined the relationship between these two conditions. METHODS We performed a case-control study at a Veterans Affairs Hospital among 709 men: 312 healthy controls, 167 men with CaP, and 229 men without CaP on prostate biopsy. Participants were asked to self-describe hair patterns at ages 30, 40 and at study enrollment. We tested the association between hair pattern (overall, vertex or frontal) and CaP status using logistic regression analysis adjusting for multiple clinical features. Disease grade was similarly examined as a secondary outcome. RESULTS Relative to healthy controls, younger age of AA onset was significantly associated with increased CaP risk (p=0.008). Similar patterns were noted for frontal (p=0.004) and vertex balding (p=0.08). When compared to biopsy negative men, a similar pattern was seen with younger age of AA onset having higher risk for CaP, though this was not significant (p=0.08). Only younger age of AA onset for frontal (p=0.05) was associated with CaP vs. biopsy negative men. However, overall balding (yes/no) was with > 2-fold increase of high-grade disease (p<0.07). CONCLUSIONS In a multiethnic cohort, men reporting earlier AA onset were at increased CaP risk and suggestively had more aggressive disease. Contrary to other studies, frontal balding was the predominant pattern associated with elevated CaP risk. Further study is required to confirm these findings in a larger sample and to better understand the role of AA, androgens, and CaP biology. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e139 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jean-Alfred Thomas Durham, NC More articles by this author Jodi A. Antonelli Durham, NC More articles by this author Lionel L. Bañez Durham, NC More articles by this author Leah Gerber Durham, NC More articles by this author Cathrine Hoyo Durham, NC More articles by this author Delores Grant Durham, NC More articles by this author Wendy Demark-Wahnefried Birmingham, AL More articles by this author Elizabeth Platz Balitmore, MD More articles by this author Elizabeth Calloway Durham, NC More articles by this author Enwono Eyoh Durham, NC More articles by this author Kathleen Shuler Durham, NC More articles by this author Stephen J. Freedland Durham, NC More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...}, number={4S}, journal={Journal of Urology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Thomas, Jean-Alfred and Antonelli, Jodi A. and Bañez, Lionel L. and Gerber, Leah and Hoyo, Cathrine and Grant, Delores and Demark-Wahnefried, Wendy and Platz, Elizabeth and Calloway, Elizabeth and Eyoh, Enwono and et al.}, year={2012}, month={Apr} }
 @article{hoyo_fortner_murtha_schildkraut_soubry_demark-wahnefried_jirtle_kurtzberg_forman_overcash_et al._2012, title={Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight}, volume={23}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/S10552-012-9932-Y}, DOI={10.1007/S10552-012-9932-Y}, abstractNote={Altered methylation at Insulin-like Growth Factor 2 (IGF2) regulatory regions has previously been associated with obesity, and several malignancies including colon, esophageal, and prostate adenocarcinomas, presumably via changes in expression and/or loss of imprinting, but the functional significance of these DNA methylation marks have not been demonstrated in humans. We examined associations among DNA methylation at IGF2 differentially methylated regions (DMRs), circulating IGF2 protein concentrations in umbilical cord blood (UCB) and birth weight in newborns. Questionnaire data were obtained from 300 pregnant women recruited between 2005 and 2009. UCB DNA methylation was measured by bisulfite pyrosequencing. UCB plasma concentrations of soluble IGF2 were measured by ELISA assays. Generalized linear regression models were used to examine the relationship between DMR methylation and IGF2 levels. Lower IGF2 DMR methylation was associated with elevated plasma IGF2 protein concentrations (β = −9.87, p < 0.01); an association that was stronger in infants born to obese women (pre-pregnancy BMI > 30 kg/m2, β = −20.21, p < 0.0001). Elevated IGF2 concentrations were associated with higher birth weight (p < 0.0001) after adjusting for maternal race/ethnicity, pre-pregnancy BMI, cigarette smoking, gestational diabetes, and infant sex. These patterns of association were not apparent at the H19 DMR. Our data suggest that variation in IGF2 DMR methylation is an important mechanism by which circulating IGF2 concentrations, a putative risk factor for obesity and cancers of the colon, esophagus, and prostate, are modulated; associations that may depend on pre-pregnancy obesity.}, number={4}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Hoyo, Cathrine and Fortner, Kimberly and Murtha, Amy P. and Schildkraut, Joellen M. and Soubry, Adelheid and Demark-Wahnefried, Wendy and Jirtle, Randy L. and Kurtzberg, Joanne and Forman, Michele R. and Overcash, Francine and et al.}, year={2012}, month={Mar}, pages={635–645} }
 @article{murphy_adigun_huang_overcash_wang_jirtle_schildkraut_murtha_iversen_hoyo_2012, title={Gender-specific methylation differences in relation to prenatal exposure to cigarette smoke}, volume={494}, ISSN={0378-1119}, url={http://dx.doi.org/10.1016/j.gene.2011.11.062}, DOI={10.1016/j.gene.2011.11.062}, abstractNote={Epigenetic alterations may mechanistically explain the developmental origins of adult disease, namely the hypothesis that many complex adult chronic diseases originate as a result of conditions encountered in utero. If true, epigenetically regulated imprinted genes, critical to normal growth and development, may partially mediate these outcomes. We determined the influence of in utero exposure to cigarette smoking on methylation at two differentially methylated regions (DMRs) regulating Insulin-like Growth Factor 2 (IGF2) and H19, and how this might relate to birth weight of infants born to 418 pregnant women. Smoking status was ascertained through self-report and medical records. Bisulfite pyrosequencing was used to measure methylation in umbilical cord blood DNAs. Least squares DNA methylation means at each DMR and birth weight were compared between infants of smokers and non-smokers, using generalized linear models. While there were no significant differences at the H19 DMR, infants born to smokers had higher methylation at the IGF2 DMR than those born to never smokers or those who quit during pregnancy (49.5%, SD=8.0 versus 46.6%, SD=5.6 and 45.8%, SD=6.3, respectively; p=0.0002). The smoking-related increase in methylation was most pronounced in male offspring (p for sex interaction=0.03), for whom approximately 20% of smoking-related low birth weight was mediated by DNA methylation at the IGF2 DMR. Our findings suggest that IGF2 DMR plasticity is an important mechanism by which in utero adjustments to environmental toxicants are conferred. Larger studies to replicate these findings are required.}, number={1}, journal={Gene}, publisher={Elsevier BV}, author={Murphy, Susan K. and Adigun, Abayomi and Huang, Zhiqing and Overcash, Francine and Wang, Frances and Jirtle, Randy L. and Schildkraut, Joellen M. and Murtha, Amy P. and Iversen, Edwin S. and Hoyo, Cathrine}, year={2012}, month={Feb}, pages={36–43} }
 @article{keku_vidal_oliver_hoyo_hall_omofoye_mcdoom_worley_galanko_sandler_et al._2012, title={Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites}, volume={23}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/S10552-012-9981-2}, DOI={10.1007/S10552-012-9981-2}, abstractNote={Evaluating genetic susceptibility may clarify effects of known environmental factors and also identify individuals at high risk. We evaluated the association of four insulin-related pathway gene polymorphisms in insulin-like growth factor-1 (IGF-I) (CA)( n ) repeat, insulin-like growth factor-2 (IGF-II) (rs680), insulin-like growth factor-binding protein-3 (IGFBP-3) (rs2854744), and adiponectin (APM1 rs1501299) with colon cancer risk, as well as relationships with circulating IGF-I, IGF-II, IGFBP-3, and C-peptide in a population-based study.Participants were African Americans (231 cases and 306 controls) and Whites (297 cases, 530 controls). Consenting subjects provided blood specimens and lifestyle/diet information. Genotyping for all genes except IGF-I was performed by the 5'-exonuclease (Taqman) assay. The IGF-I (CA)(n) repeat was assayed by PCR and fragment analysis. Circulating proteins were measured by enzyme immunoassays. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated by logistic regression.The IGF-I (CA)( 19 ) repeat was higher in White controls (50 %) than African American controls (31 %). Whites homozygous for the IGF-I (CA)(19) repeat had a nearly twofold increase in risk of colon cancer (OR = 1.77; 95 % CI = 1.15-2.73), but not African Americans (OR = 0.73, 95 % CI 0.50-1.51). We observed an inverse association between the IGF-II Apa1 A-variant and colon cancer risk (OR = 0.49, 95 % CI 0.28-0.88) in Whites only. Carrying the IGFBP-3 variant alleles was associated with lower IGFBP-3 protein levels, a difference most pronounced in Whites (p-trend <0.05).These results support an association between insulin pathway-related genes and elevated colon cancer risk in Whites but not in African Americans.}, number={7}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Keku, Temitope O. and Vidal, Adriana and Oliver, Shannon and Hoyo, Catherine and Hall, Ingrid J. and Omofoye, Oluwaseun and McDoom, Maya and Worley, Kendra and Galanko, Joseph and Sandler, Robert S. and et al.}, year={2012}, month={May}, pages={1127–1138} }
 @article{perkins_murphy_murtha_schildkraut_jirtle_demark-wahnefried_forman_kurtzberg_overcash_huang_et al._2012, title={Insulin-Like Growth Factor 2/H19 Methylation at Birth and Risk of Overweight and Obesity in Children}, volume={161}, ISSN={0022-3476}, url={http://dx.doi.org/10.1016/j.jpeds.2012.01.015}, DOI={10.1016/j.jpeds.2012.01.015}, abstractNote={To determine whether aberrant DNA methylation at differentially methylated regions (DMRs) regulating insulin-like growth factor 2 (IGF2) expression in umbilical cord blood is associated with overweight or obesity in a multiethnic cohort.Umbilical cord blood leukocytes of 204 infants born between 2005 and 2009 in Durham, North Carolina, were analyzed for DNA methylation at two IGF2 DMRs by using pyrosequencing. Anthropometric and feeding data were collected at age 1 year. Methylation differences were compared between children >85th percentile of the Centers for Disease Control and Prevention growth charts weight-for-age (WFA) and children ≤ 85th percentile of WFA at 1 year by using generalized linear models, adjusting for post-natal caloric intake, maternal cigarette smoking, and race/ethnicity.The methylation percentages at the H19 imprint center DMR was higher in infants with WFA >85th percentile (62.7%; 95% CI, 59.9%-65.5%) than in infants with WFA ≤ 85th percentile (59.3%; 95% CI, 58.2%-60.3%; P = .02). At the intragenic IGF2 DMR, methylation levels were comparable between infants with WFA ≤ 85th percentile and infants with WFA >85th percentile.Our findings suggest that IGF2 plasticity may be mechanistically important in early childhood overweight or obese status. If confirmed in larger studies, these findings suggest aberrant DNA methylation at sequences regulating imprinted genes may be useful identifiers of children at risk for the development of early obesity.}, number={1}, journal={The Journal of Pediatrics}, publisher={Elsevier BV}, author={Perkins, Ellen and Murphy, Susan K. and Murtha, Amy P. and Schildkraut, Joellen and Jirtle, Randy L. and Demark-Wahnefried, Wendy and Forman, Michele R. and Kurtzberg, Joanne and Overcash, Francine and Huang, Zhiqing and et al.}, year={2012}, month={Jul}, pages={31–39} }
 @article{masko_moreira_bañez_hoyo_grant_calloway_shuler_newman_gaines_taylor_et al._2011, title={1613 GENETIC VARIATION IN OBESITY-RELATED GENES ADBR2, ADBR3, GHRL, HSD11B1, AND SHC1 AND RISK OF PROSTATE CANCER: A VA CASE-CONTROL STUDY}, volume={185}, ISSN={0022-5347 1527-3792}, url={http://dx.doi.org/10.1016/j.juro.2011.02.1721}, DOI={10.1016/j.juro.2011.02.1721}, abstractNote={You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 20111613 GENETIC VARIATION IN OBESITY-RELATED GENES ADBR2, ADBR3, GHRL, HSD11B1, AND SHC1 AND RISK OF PROSTATE CANCER: A VA CASE-CONTROL STUDY Elizabeth M. Masko, Daniel M. Moreira, Lionel L. Bañez, Cathrine Hoyo, Delores J. Grant, Elizabeth E. Calloway, Kathleen H. Shuler, Kathryn A. Newman, Alexis R. Gaines, Loretta A. Taylor, Cary N. Robertson, and Stephen J. Freedland Elizabeth M. MaskoElizabeth M. Masko Durham, NC More articles by this author , Daniel M. MoreiraDaniel M. Moreira New Hyde Park, NY More articles by this author , Lionel L. BañezLionel L. Bañez Durham, NC More articles by this author , Cathrine HoyoCathrine Hoyo Durham, NC More articles by this author , Delores J. GrantDelores J. Grant Durham, NC More articles by this author , Elizabeth E. CallowayElizabeth E. Calloway Durham, NC More articles by this author , Kathleen H. ShulerKathleen H. Shuler Durham, NC More articles by this author , Kathryn A. NewmanKathryn A. Newman Durham, NC More articles by this author , Alexis R. GainesAlexis R. Gaines Durham, NC More articles by this author , Loretta A. TaylorLoretta A. Taylor Durham, NC More articles by this author , Cary N. RobertsonCary N. Robertson Durham, NC More articles by this author , and Stephen J. FreedlandStephen J. Freedland Durham, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1721AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Single nucleotide polymorphisms (SNPs) are single nucleotide variations that occur within alleles among individuals. It is believed that SNPs may predispose a person to diseases such as obesity or cancer. One study showed that SNPs within genes linked with obesity were also associated with breast cancer risk. As prostate cancer (PC) mortality is linked with obesity, we determined if SNPs within 5 obesity-related genes were also linked to PC risk in a similar manner to the breast cancer study. METHODS A total of 53 SNPs were tagged in the genes ADBR2, ADBR3, GHRL, HSD11B1, and SHC1 using the program HAPMAP. DNA collected from 216 subjects (108 incident cases, 108 “healthy” controls) from the Durham VA Hospital were then genotyped for these SNPs. Cases and controls were frequency matched on age and BMI. Logistic regression models were used to determine the risk of obesity (BMI >30 kg/m2) and PC (and high-grade defined as Gleason >7 vs. low-grade/control) for each SNP, adjusting for age and race. RESULTS In our study population, 83 men were Caucasian and 133 African American. There was no significant differences in age (p=0.18), race (p=0.96), and BMI (p=0.12) for cases and controls. Among the 53 SNPs genotyped, 5 SNPs in ADRB2, ADRB3, and SHC1 were associated with an increased risk of PC (OR 1.88–2.21; p=0.01–0.04), particularly high-grade disease (OR 2.50–3.26; p=0.0004–0.05). Another 4 SNPs in ADRB2 and HSD11B1 were associated with a decreased risk of PC (p=0.01–0.05). A total of 7 SNPs were associated with an increased risk of obesity (p=0.004–0.02). CONCLUSIONS In this small pilot study, we found 14 of the 53 analyzed single SNPs in genes previously linked with obesity that were associated with PC risk, both positively and negatively at an alpha of <0.05. This is more than the 3 SNPs that would be predicted based upon random chance. Future studies will validate these results in an independent cohort, with the hope of further confirming SNPs that may be used for personalized medicine as well as providing a genetic link between obesity and PC. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e647 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Elizabeth M. Masko Durham, NC More articles by this author Daniel M. Moreira New Hyde Park, NY More articles by this author Lionel L. Bañez Durham, NC More articles by this author Cathrine Hoyo Durham, NC More articles by this author Delores J. Grant Durham, NC More articles by this author Elizabeth E. Calloway Durham, NC More articles by this author Kathleen H. Shuler Durham, NC More articles by this author Kathryn A. Newman Durham, NC More articles by this author Alexis R. Gaines Durham, NC More articles by this author Loretta A. Taylor Durham, NC More articles by this author Cary N. Robertson Durham, NC More articles by this author Stephen J. Freedland Durham, NC More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...}, number={4S}, journal={Journal of Urology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Masko, Elizabeth M. and Moreira, Daniel M. and Bañez, Lionel L. and Hoyo, Cathrine and Grant, Delores J. and Calloway, Elizabeth E. and Shuler, Kathleen H. and Newman, Kathryn A. and Gaines, Alexis R. and Taylor, Loretta A. and et al.}, year={2011}, month={Apr} }
 @article{bañez_hoyo_masko_calloway_shuler_newman_gaines_freedland_robertson_2011, title={605 COMBINATION OF
            ADH
            GENE POLYMORPHISM AND ALCOHOL CONSUMPTION CONSTITUTES A NOVEL PROSTATE CANCER RISK FACTOR IN AFRICAN-AMERICAN MEN}, volume={185}, ISSN={0022-5347 1527-3792}, url={http://dx.doi.org/10.1016/j.juro.2011.02.1458}, DOI={10.1016/j.juro.2011.02.1458}, abstractNote={You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 2011605 COMBINATION OF ADH GENE POLYMORPHISM AND ALCOHOL CONSUMPTION CONSTITUTES A NOVEL PROSTATE CANCER RISK FACTOR IN AFRICAN-AMERICAN MEN Lionel L. Bañez, Cathrine Hoyo, Elizabeth M. Masko, Elizabeth E. Calloway, Kathleen H. Shuler, Kathryn A. Newman, Alexis R. Gaines, Stephen J. Freedland, and Cary N. Robertson Lionel L. BañezLionel L. Bañez Durham, NC More articles by this author , Cathrine HoyoCathrine Hoyo Durham, NC More articles by this author , Elizabeth M. MaskoElizabeth M. Masko Durham, NC More articles by this author , Elizabeth E. CallowayElizabeth E. Calloway Durham, NC More articles by this author , Kathleen H. ShulerKathleen H. Shuler Durham, NC More articles by this author , Kathryn A. NewmanKathryn A. Newman Durham, NC More articles by this author , Alexis R. GainesAlexis R. Gaines Durham, NC More articles by this author , Stephen J. FreedlandStephen J. Freedland Durham, NC More articles by this author , and Cary N. RobertsonCary N. Robertson Durham, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1458AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES African-American men (AAM) are at higher risk for prostate cancer (PC) vs. Caucasian men (CM). The cause is likely multi-factorial. Though alcohol intake as a PC risk factor in the overall population is controversial, we recently reported that, among men undergoing prostate biopsy, alcohol intake was associated with increased PC risk only among AAM. Polymorphisms of the alcohol dehydrogenase (ADH) gene, that lead to bodily accumulation of acetaldehyde - a carcinogen, occur more frequently in AAM. Whether these alleles interact with alcohol exposure to promote PC development is unknown. METHODS DNA and alcohol intake surveys were obtained from 347 men from the Durham VA Hospital who underwent prostate biopsy (n=199) or were hospital-based controls (n=148 with no indication for biopsy) from 2007 to 2010. The DNA was genotyped for ADH1B*3 and dichotomized into carriers of the common allele (ADH1B*3-; C/C) and the variant allele (ADH1B*3+; C/T or T/T). Alcohol intake was dichotomized into non-drinker and alcohol drinker. Two separate logistic regression models, adjusting for clinical covariates, were conducted: 1) Only among men who underwent a biopsy; 2) Comparing men with cancer on biopsy to the controls. RESULTS A total of 60 (13%) men were heterozygous and 11 (2%) were homozygous for ADH1B*3. Nearly all ADH1B*3+ subjects were AAM (n=69; 97%) with 35% of AAM carrying the variant allele. ADH1B*3+ alcohol drinkers were ∼4 times more likely to have a positive biopsy than ADH1B*3- non-drinkers (OR=3.7, 95%CI=1.0–13.3). In crude analysis comparing biopsy+ men to controls, ADH1B*3+ alcohol drinkers were 5 times more likely to have PC than ADH1B*3- non-drinkers. There was a trend for increased PC risk among ADH1B*3+ alcohol drinkers in multivariate analyses which did not reach statistical significance (p=0.11). In all models, PC risk for ADH1B*3+ non-drinkers and ADH1B*3- alcohol drinkers were not different from ADH1B*3- non-drinkers. CONCLUSIONS Our preliminary findings suggest the ADH1B*3 variant allele and alcohol intake is a novel gene-environment interaction for PC risk, nearly unique to AAM. If confirmed, this gene-environment interaction may help explain increased PC risk in AAM who consume alcohol, while no effect is seen in CM. Table 1. Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer among risk groups based on ADH1B*3 genotype and alcohol intake Biopsy(+) vs. Biopsy(-) Biopsy(+) vs. Biopsy(-) Biopsy(+) vs. Controls Biopsy(+) vs. Controls Crude Adjusted⁎ Crude Adjusted⁎⁎ ADH1B*3 Alcohol OR (95% CI) p OR (95% CI) p OR (95% CI) p OR (95% CI) p (-) (-) Ref Ref Ref Ref (+) (+) 4.36(1.36-13.94) 0.02 3.67(1.02-13.28) 0.047 5.21(1.64-16.61) 0.005 3.08(0.77-12.25) 0.11 (+) (-) 1.24(0.47-3.31) 0.67 1.01(0.34-3.05) 0.98 1.60(0.60-4.29) 0.35 1.77(0.51-6.15) 0.37 (-) (+) 1.70(0.89-3.24) 0.10 1.85(0.91-3.73) 0.09 1.46(0.89-3.60) 0.22 1.57(0.75-3.38) 0.23 ⁎ adjusted for age, race, PSA, body mass index and year of biopsy; ⁎⁎ adjusted for age, race, BMI and year of enrollment © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e244 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lionel L. Bañez Durham, NC More articles by this author Cathrine Hoyo Durham, NC More articles by this author Elizabeth M. Masko Durham, NC More articles by this author Elizabeth E. Calloway Durham, NC More articles by this author Kathleen H. Shuler Durham, NC More articles by this author Kathryn A. Newman Durham, NC More articles by this author Alexis R. Gaines Durham, NC More articles by this author Stephen J. Freedland Durham, NC More articles by this author Cary N. Robertson Durham, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...}, number={4S}, journal={Journal of Urology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Bañez, Lionel L. and Hoyo, Cathrine and Masko, Elizabeth M. and Calloway, Elizabeth E. and Shuler, Kathleen H. and Newman, Kathryn A. and Gaines, Alexis R. and Freedland, Stephen J. and Robertson, Cary N.}, year={2011}, month={Apr} }
 @article{williams_whitley_hoyo_grant_iraggi_newman_gerber_taylor_mckeever_freedland_2011, title={A high ratio of dietary n-6/n-3 polyunsaturated fatty acids is associated with increased risk of prostate cancer}, volume={31}, ISSN={0271-5317}, url={http://dx.doi.org/10.1016/j.nutres.2011.01.002}, DOI={10.1016/j.nutres.2011.01.002}, abstractNote={Experimental studies suggest omega-3 (n-3) polyunsaturated fatty acids (PUFA) suppress and n-6 PUFA promote prostate tumor carcinogenesis. Epidemiologic evidence remains inconclusive. The objectives of this study were to examine the association between n-3 and n-6 PUFA and prostate cancer risk and determine if these associations differ by race or disease aggressiveness. We hypothesize that high intakes of n-3 and n-6 PUFA will be associated with lower and higher prostate cancer risk, respectively. A case-control study comprising 79 prostate cancer cases and 187 controls was conducted at the Durham VA Medical Center. Diet was assessed using a food frequency questionnaire. Logistic regression analyses were used to obtain odds ratios (ORs) and 95% confidence intervals (95% CI) for the associations between n-3 and n-6 PUFA intakes, the dietary ratio of n-6/n-3 fatty acids, and prostate cancer risk. Our results showed no significant associations between specific n-3 or n-6 PUFA intakes and prostate cancer risk. The highest dietary ratio of n-6/n-3 was significantly associated with elevated risk of high-grade (OR, 3.55; 95% CI, 1.18-10.69; P(trend) = 0.03), but not low-grade prostate cancer (OR, 0.95; 95% CI, 0.43-2.17). In race-specific analyses, an increasing dietary ratio of n-6/n-3 fatty acids correlated with higher prostate cancer risk among white men (P(trend) = 0.05), but not black men. In conclusion, our findings suggest that a high dietary ratio of n-6/n-3 fatty acids may increase the risk of overall prostate cancer among white men and possibly increase the risk of high-grade prostate cancer among all men.}, number={1}, journal={Nutrition Research}, publisher={Elsevier BV}, author={Williams, Christina D. and Whitley, Brian M. and Hoyo, Cathrine and Grant, Delores J. and Iraggi, Jared D. and Newman, Kathryn A. and Gerber, Leah and Taylor, Loretta A. and McKeever, Madeline G. and Freedland, Stephen J.}, year={2011}, month={Jan}, pages={1–8} }
 @article{moreira_anderson_gerber_thomas_bañez_mckeever_hoyo_grant_jayachandran_freedland_2011, title={The association of diabetes mellitus and high-grade prostate cancer in a multiethnic biopsy series}, volume={22}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/s10552-011-9770-3}, DOI={10.1007/s10552-011-9770-3}, number={7}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Moreira, Daniel M. and Anderson, Tiffany and Gerber, Leah and Thomas, Jean-Alfred and Bañez, Lionel L. and McKeever, Madeline G. and Hoyo, Cathrine and Grant, Delores and Jayachandran, Jayakrishnan and Freedland, Stephen J.}, year={2011}, month={May}, pages={977–983} }
 @article{fortner_murtha_hoyo_overcash_huang_schildkraut_kurtzberg_jirtle_forman_murphy_2009, title={70: Epigenetic orchestration of circulating insulin-like growth factor-2 levels in cord blood}, volume={201}, ISSN={0002-9378}, url={http://dx.doi.org/10.1016/j.ajog.2009.10.085}, DOI={10.1016/j.ajog.2009.10.085}, number={6}, journal={American Journal of Obstetrics and Gynecology}, publisher={Elsevier BV}, author={Fortner, Kimberly and Murtha, Amy and Hoyo, Cathrine and Overcash, Francine and Huang, Zhiquing and Schildkraut, Joellen and Kurtzberg, Joanne and Jirtle, Randy and Forman, Michele and Murphy, Susan}, year={2009}, month={Dec}, pages={S39} }
 @article{antonelli_jones_bañez_thomas_anderson_taylor_gerber_anderson_hoyo_grant_et al._2009, title={Exercise and Prostate Cancer Risk in a Cohort of Veterans Undergoing Prostate Needle Biopsy}, volume={182}, ISSN={0022-5347 1527-3792}, url={http://dx.doi.org/10.1016/j.juro.2009.07.028}, DOI={10.1016/j.juro.2009.07.028}, abstractNote={No AccessJournal of UrologyAdult Urology1 Nov 2009Exercise and Prostate Cancer Risk in a Cohort of Veterans Undergoing Prostate Needle Biopsyis accompanied byCan Men Reduce the Risk of Prostate Cancer Through Lifestyle Changes? Jodi A. Antonelli, Lee W. Jones, Lionel L. Bañez, Jean-Alfred Thomas, Kelly Anderson, Loretta A. Taylor, Leah Gerber, Tiffany Anderson, Catherine Hoyo, Delores Grant, and Stephen J. Freedland Jodi A. AntonelliJodi A. Antonelli Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author , Lee W. JonesLee W. Jones Robert Preston Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina More articles by this author , Lionel L. BañezLionel L. Bañez Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author , Jean-Alfred ThomasJean-Alfred Thomas Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author , Kelly AndersonKelly Anderson Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author , Loretta A. TaylorLoretta A. Taylor Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author , Leah GerberLeah Gerber Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author , Tiffany AndersonTiffany Anderson Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina JLC-Biomedical/Biotechnology Research Institute, Cancer Research Program, North Carolina Central University, Durham, North Carolina More articles by this author , Catherine HoyoCatherine Hoyo Department of Surgery, Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina More articles by this author , Delores GrantDelores Grant JLC-Biomedical/Biotechnology Research Institute, Cancer Research Program, North Carolina Central University, Durham, North Carolina More articles by this author , and Stephen J. FreedlandStephen J. Freedland Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Department of Pathology, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2009.07.028AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Epidemiological and molecular evidence suggest potential associations between exercise and prostate cancer risk reduction. We further characterized this relationship by examining exercise and cancer risk among men undergoing prostate needle biopsy. Materials and Methods: A total of 190 men who underwent prostate biopsy at the Durham Veterans Affairs Medical Center completed a questionnaire on current exercise behavior. Participants were asked average frequency of mild, moderate and strenuous intensity exercise in a typical week, as well as average duration as assessed by the Godin Leisure Time Exercise Questionnaire. Total current exercise was calculated in terms of metabolic equivalent task hours per week. Primary outcome measures were prostate biopsy result and Gleason sum. Results: After adjusting for age, race, body mass index, prostate specific antigen, digital rectal examination, family history, previous prostate biopsy and comorbidity score, men who reported 9 or more metabolic equivalent task hours per week of exercise were significantly less likely to have cancer on biopsy (OR 0.35, CI 0.17–0.75, p = 0.007). Furthermore, among men with malignant biopsy results, reporting moderate exercise (3 to 8.9 metabolic equivalent task hours weekly) was associated with a lower risk of high grade disease (Gleason 7 or greater, OR 0.14, CI 0.02–0.94, p = 0.04). Conclusions: To our knowledge these results provide the first evidence of an association between exercise and prostate cancer risk as well as grade at diagnosis in men scheduled to undergo prostate biopsy. Specifically moderate exercise was associated with a lower risk of prostate cancer and in men with cancer, lower grade disease. Further investigation using an objective measure of exercise in a larger sample size is required to confirm these findings. References 1 : A mechanism to explain how regular exercise might reduce the risk for clinical prostate cancer. Eur J Cancer Prev2007; 16: 415. Google Scholar 2 : Exercise alters the IGF axis in vivo and increases p53 protein in prostate tumor cells in vitro. J Appl Physiol2004; 96: 450. Google Scholar 3 : Intensive lifestyle changes may affect the progression of prostate cancer. J Urol2005; 174: 1065. Link, Google Scholar 4 : Exercise and hormesis: activation of cellular antioxidant signaling pathway. Ann N Y Acad Sci2006; 1067: 425. Google Scholar 5 : Oxidative stress: from basic research to clinical application. Am J Med1991; 91: 31S. Google Scholar 6 : Prostate stem cell antigen vaccination induces a long-term protective immune response against prostate cancer in the absence of autoimmunity. Cancer Res2008; 68: 861. Google Scholar 7 : Physical exercise and immune system function in cancer survivors: a comprehensive review and future directions. Cancer2002; 94: 539. Google Scholar 8 : Lifetime occupational physical activity and incidental prostate cancer (Canada). Cancer Causes Control2000; 11: 759. Google Scholar 9 : A prospective study of physical activity and incident and fatal prostate cancer. Arch Intern Med2005; 165: 1005. Google Scholar 10 : Physical activity in relation to total, advanced, and fatal prostate cancer. Cancer Epidemiol Biomarkers Prev2008; 17: 2458. Google Scholar 11 : Occupational physical activity and risk for prostate cancer in a nationwide cohort study in Sweden. Br J Cancer2002; 86: 70. Google Scholar 12 : A prospective cohort study of physical activity and body size in relation to prostate cancer risk (United States). Cancer Causes Control2001; 12: 187. Google Scholar 13 : Association of smoking, body mass, and physical activity with risk of prostate cancer in the Iowa 65+ Rural Health Study (United States). Cancer Causes Control1997; 8: 229. Google Scholar 14 : Assessment of leisure time exercise behavior by self-report: a concurrent validity study. Can J Public Health1986; 77: 359. Google Scholar 15 : Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc2007; 39: 1423. Google Scholar 16 : Physical activity and survival after breast cancer diagnosis. JAMA2005; 293: 2479. Google Scholar 17 : A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis1987; 40: 373. Crossref, Medline, Google Scholar 18 : Exercise therapy across the prostate cancer continuum. Prostate Cancer Prostatic Dis2009; 12: 110. Google Scholar 19 : Mechanisms linking physical activity with cancer. Nat Rev Cancer2008; 8: 205. Google Scholar 20 : Lifetime occupational and recreational physical activity and risk of benign prostatic hyperplasia. Int J Cancer2006; 118: 2632. Google Scholar 21 : Effects of running distance and performance on incident benign prostatic hyperplasia. Med Sci Sports Exerc2008; 40: 1733. Google Scholar © 2009 by American Urological AssociationFiguresReferencesRelatedDetailsRelated articlesJournal of Urology16 Sep 2009Can Men Reduce the Risk of Prostate Cancer Through Lifestyle Changes? Volume 182Issue 5November 2009Page: 2226-2231 Advertisement Copyright & Permissions© 2009 by American Urological AssociationKeywordsrisk factorsprostatic neoplasmsexerciseMetricsAuthor Information Jodi A. Antonelli Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author Lee W. Jones Robert Preston Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina More articles by this author Lionel L. Bañez Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author Jean-Alfred Thomas Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author Kelly Anderson Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author Loretta A. Taylor Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author Leah Gerber Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author Tiffany Anderson Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina JLC-Biomedical/Biotechnology Research Institute, Cancer Research Program, North Carolina Central University, Durham, North Carolina More articles by this author Catherine Hoyo Department of Surgery, Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina More articles by this author Delores Grant JLC-Biomedical/Biotechnology Research Institute, Cancer Research Program, North Carolina Central University, Durham, North Carolina More articles by this author Stephen J. Freedland Duke Prostate Center, Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina Department of Pathology, Duke University Medical Center, Durham, North Carolina Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina More articles by this author Expand All Advertisement PDF downloadLoading ...}, number={5}, journal={Journal of Urology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Antonelli, Jodi A. and Jones, Lee W. and Bañez, Lionel L. and Thomas, Jean-Alfred and Anderson, Kelly and Taylor, Loretta A. and Gerber, Leah and Anderson, Tiffany and Hoyo, Catherine and Grant, Delores and et al.}, year={2009}, month={Nov}, pages={2226–2231} }
 @article{hoyo_schildkraut_murphy_chow_vaughan_risch_marks_jirtle_calingeart_mayne_et al._2009, title={IGF2Rpolymorphisms and risk of esophageal and gastric adenocarcinomas}, volume={125}, ISSN={0020-7136 1097-0215}, url={http://dx.doi.org/10.1002/ijc.24623}, DOI={10.1002/ijc.24623}, abstractNote={The mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes a protein that plays a critical role in tumor suppression, in part by modulating bioavailability of a potent mitogen, insulin-like growth factor-2 (IGF2). We tested the hypothesis that the common nonsynonymous genetic variants in M6P/IGF2R c.901C > G (Leu > Val) in exon 6 and c.5002G > A (Gly > Arg) in exon 34 are associated with risk of esophageal and gastric cancers. Study participants in this population-based study comprise 197 controls and 182 cases, including 105 with esophageal-gastric cardia adenocarcinoma (EGA), 57 with noncardia gastric adenocarcinoma and 20 with esophageal squamous (ES) cell carcinoma. Among white males, odds ratios (ORs) were elevated in relation to carrying at least 1 c.901C > G allele for EGA [OR = 1.9; 95% confidence intervals (CIs) = 1.0–3.6] and noncardia gastric cancer (OR = 2.5; 95% CI = 1.2–5.5), but not ES. Exploratory subgroup analyses suggested that associations between EGA and this variant were stronger among irregular or nonusers of nonsteroidal anti-inflammatory drugs (NSAIDs) (OR = 2.3; 95% CI = 1.2–4.2) and cigarette smokers (OR = 2.1; 95% CI = 1.0–4.2). An association between carrying the c.5002G > A genotype and EGA was not evident. These findings suggest that nonsynonymous polymorphisms in M6P/IGF2R may contribute to the risks of EGA and noncardia adenocarcinomas. Larger studies are required to confirm these findings. © 2009 UICC}, number={11}, journal={International Journal of Cancer}, publisher={Wiley}, author={Hoyo, Cathrine and Schildkraut, Joellen M. and Murphy, Susan K. and Chow, Wong-Ho and Vaughan, Thomas L. and Risch, Harvey and Marks, Jeffrey R. and Jirtle, Randy L. and Calingeart, Brian and Mayne, Susan and et al.}, year={2009}, month={Dec}, pages={2673–2678} }
 @article{hoyo_grubber_demark-wahnefried_lobaugh_jeffreys_grambow_marks_keku_walther_schildkraut_2009, title={Predictors of Variation in Serum IGFI and IGFBP3 Levels in Healthy African American and White Men}, volume={101}, ISSN={0027-9684}, url={http://dx.doi.org/10.1016/S0027-9684(15)30981-0}, DOI={10.1016/S0027-9684(15)30981-0}, abstractNote={Individual variation in circulating insulinlike growth factor-1 (IGF1) and its major binding protein, insulinlike growth factor binding protein-3 (IGFBP3), have been etiologically linked to several chronic diseases, including some cancers. Factors associated with variation in circulating levels of these peptide hormones remain unclear.Multiple linear regression models were used to determine the extent to which sociodemographic characteristics, lifestyle factors, personal and family history of chronic disease, and common genetic variants, the (CA)n repeat polymorphism in the IGF1 promoter and the IGFBP3-202 A/C polymorphism (rs2854744) predict variation in IGF1 or IGFBP3 serum levels in 33 otherwise healthy African American and 37 white males recruited from Durham Veterans Administration Medical Center.Predictors of serum IGF1, IGFBP3, and the IGF1:IGFBP3 molar ratio varied by race. In African Americans, 17% and 28% of the variation in serum IGF1 and the IGF1:IGFBP3 molar ratio, were explained by cigarette smoking and carrying the IGF1 (CA)19 repeat allele, respectively. Not carrying at least 1 IGF1 (CA)19 repeat allele and a high body mass index explained 8% and 14%, respectively, of the variation IGFBP3 levels. These factors did not predict variation of these peptides in whites.If successfully replicated in larger studies, these findings would add to recent evidence, suggesting known genetic and lifestyle chronic disease risk factors influence IGF1 and IGFBP3 circulating levels differently in African Americans and whites.}, number={7}, journal={Journal of the National Medical Association}, publisher={Elsevier BV}, author={Hoyo, Cathrine and Grubber, Janet and Demark-Wahnefried, Wendy and Lobaugh, Bruce and Jeffreys, Amy S. and Grambow, Steven C. and Marks, Jeffrey R. and Keku, Temitope O. and Walther, Phillip J. and Schildkraut, Joellen M.}, year={2009}, month={Jul}, pages={711–716} }
 @article{hoyo_yarnall_fortney_2007, title={Short birth intervals and uterine cervical cancer risk in Jamaican women}, volume={98}, ISSN={0020-7292}, url={http://dx.doi.org/10.1016/j.ijgo.2007.04.010}, DOI={10.1016/j.ijgo.2007.04.010}, abstractNote={High parity common in developing countries has been consistently associated with higher cervical cancer (CC) risk. Pregnancy-related immunosuppression has been proposed as a possible mechanism by which oncogenic human papillomavirus (HPV) can replicate. Stanczuck reported a higher risk of CC among women genetically predisposed to lower immune response. In-vitro studies also demonstrate increased transcriptional activity of HPV16/18 in a progesterone-rich environment. Indeed a greater than 2-fold increase in CC risk was reported in women with rapid multiple births. However this study used nulliparous women as referents which does not allow one to distinguish the role of parity from that of birth-intervals. Birth-intervals are a modifiable risk factor of CC 80% of which occurs in developing countries. To determine whether short birth-intervals increase CC risk incident cases were identified through the Kingston-St. Andrews Jamaica Cancer Registry and controls were identified from cytology log-books of facilities where cases were diagnosed. Response rates of cases and controls were 82% and 60% respectively. Analyses are restricted to 183 cases and 214 controls with >/= 2 pregnancies each lasting >/= 7 months (>/=1 birth interval). The average interval was estimated by dividing the sum of non-pregnant months by total pregnancies. We assessed factors known to be associated with CC or pregnancy for confounding and retained those that changed the OR >/= 10%. (excerpt)}, number={1}, journal={International Journal of Gynecology & Obstetrics}, publisher={Wiley}, author={Hoyo, C. and Yarnall, K.S.H. and Fortney, J.}, year={2007}, month={May}, pages={56–57} }
 @article{hoyo_berchuck_halabi_bentley_moorman_calingaert_schildkraut_2005, title={Anthropometric Measurements and Epithelial Ovarian Cancer Risk in African–American and White women}, volume={16}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/s10552-005-3205-y}, DOI={10.1007/s10552-005-3205-y}, number={8}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Hoyo, Cathrine and Berchuck, Andrew and Halabi, Susan and Bentley, Rex C. and Moorman, Patricia and Calingaert, Brian and Schildkraut, Joellen M.}, year={2005}, month={Oct}, pages={955–963} }
 @article{hoyo_yarnall_skinner_moorman_sellers_reid_2005, title={Pain predicts non-adherence to pap smear screening among middle-aged African American women}, volume={41}, ISSN={0091-7435}, url={http://dx.doi.org/10.1016/j.ypmed.2004.11.021}, DOI={10.1016/j.ypmed.2004.11.021}, abstractNote={Middle-aged African American women have the highest incidence and mortality of invasive cervical cancer in the United States and the lowest adherence to pap smear screening.In 2001, we identified factors associated with non-adherence to screening recommendations using three focus group interviews and subsequently developed a questionnaire administered to 144 African American women aged 45 to 65 years.The perception that the Pap test was painful was associated with non-adherence to screening recommendations (OR = 4.78; 95%CI: 1.67-13.7). Difficulty to pay for the office visit coupled with perceived pain was associated with a nearly sixfold increase in risk of non-adherence (OR = 5.8; 95%CI: 2.8-15.5). Previously identified barriers to screening including lower education and socioeconomic status, poor access to care, knowledge of and exposure to known risk factors of invasive cervical cancer, cancer fatalism, and perceived racism were not independently associated with non-adherence.These data suggest that, among middle-aged African American women, future interventions addressing pain during a Pap test will likely increase acceptability of and adherence to cervical cancer screening. Pain could be addressed either by providing information during the pap test and/or using smaller lubricated speculums.}, number={2}, journal={Preventive Medicine}, publisher={Elsevier BV}, author={Hoyo, Cathrine and Yarnall, Kimberly S.H. and Skinner, Celette Sugg and Moorman, Patricia G. and Sellers, Denethia and Reid, LaVerne}, year={2005}, month={Aug}, pages={439–445} }