@article{cevik_skaar_jima_liu_ostbye_whitson_jirtle_hoyo_planchart_2024, title={DNA methylation of imprint control regions associated with Alzheimer's disease in non-Hispanic Blacks and non-Hispanic Whites}, volume={16}, ISSN={["1868-7083"]}, DOI={10.1186/s13148-024-01672-4}, abstractNote={Alzheimer's disease (AD) prevalence is twice as high in non-Hispanic Blacks (NHBs) as in non-Hispanic Whites (NHWs). The objective of this study was to determine whether aberrant methylation at imprint control regions (ICRs) is associated with AD. Differentially methylated regions (DMRs) were bioinformatically identified from whole-genome bisulfite sequenced DNA derived from brain tissue of 9 AD (5 NHBs and 4 NHWs) and 8 controls (4 NHBs and 4 NHWs). We identified DMRs located within 120 regions defined as candidate ICRs in the human imprintome ( https://genome.ucsc.edu/s/imprintome/hg38.AD.Brain_track ). Eighty-one ICRs were differentially methylated in NHB-AD, and 27 ICRs were differentially methylated in NHW-AD, with two regions common to both populations that are proximal to the inflammasome gene, NLRP1, and a known imprinted gene, MEST/MESTIT1. These findings indicate that early developmental alterations in DNA methylation of regions regulating genomic imprinting may contribute to AD risk and that this epigenetic risk differs between NHBs and NHWs.}, number={1}, journal={CLINICAL EPIGENETICS}, author={Cevik, Sebnem E. and Skaar, David A. and Jima, Dereje D. and Liu, Andy J. and Ostbye, Truls and Whitson, Heather E. and Jirtle, Randy L. and Hoyo, Cathrine and Planchart, Antonio}, year={2024}, month={Apr} }
 @article{vidal_chandramouli_marchesoni_brown_liu_murphy_maguire_wang_abdelmalek_mavis_et al._2023, title={<i>AHRR</i> Hypomethylation mediates the association between maternal smoking and metabolic profiles in children}, volume={7}, ISSN={["2471-254X"]}, DOI={10.1097/HC9.0000000000000243}, abstractNote={
            Background:
            Tobacco smoking during pregnancy is associated with metabolic dysfunction in children, but mechanistic insights remain limited. Hypomethylation of cg05575921 in the aryl hydrocarbon receptor repressor (AHRR) gene is associated with in utero tobacco smoke exposure. In this study, we evaluated whether AHRR hypomethylation mediates the association between maternal smoking and metabolic dysfunction in children.
          
          
            Methods:
            We assessed metabolic dysfunction using liver fat content (LFC), serum, and clinical data in children aged 7–12 years (n=78) followed since birth. Maternal smoking was self-reported at 12 weeks gestation. Methylation was measured by means of pyrosequencing at 3 sequential CpG sites, including cg05575921, at birth and at ages 7–12. Regression models were used to evaluate whether AHRR methylation mediated the association between maternal smoking and child metabolic dysfunction.
          
          
            Results:
            Average AHRR methylation at birth was significantly higher among children of nonsmoking mothers compared with children of mothers who smoked (69.8% ± 4.4% vs. 63.5% ± 5.5, p=0.0006). AHRR hypomethylation at birth was associated with higher liver fat content (p=0.01), triglycerides (p=0.01), and alanine aminotransferase levels (p=0.03), and lower HDL cholesterol (p=0.01) in childhood. AHRR hypomethylation significantly mediated associations between maternal smoking and liver fat content (indirect effect=0.213, p=0.018), triglycerides (indirect effect=0.297, p=0.044), and HDL cholesterol (indirect effect = -0.413, p=0.007). AHRR methylation in childhood (n=78) was no longer significantly associated with prenatal smoke exposure or child metabolic parameters (p>0.05).
          
          
            Conclusions:
            
                                 AHRR hypomethylation significantly mediates the association between prenatal tobacco smoke exposure and features of childhood metabolic dysfunction, despite the lack of persistent hypomethylation of AHRR into childhood. Further studies are needed to replicate these findings and to explore their causal and long-term significance.
          }, number={10}, journal={HEPATOLOGY COMMUNICATIONS}, author={Vidal, Adriana C. and Chandramouli, Shivram A. and Marchesoni, Joddy and Brown, Nia and Liu, Yukun and Murphy, Susan K. and Maguire, Rachel and Wang, Yaxu and Abdelmalek, Manal F. and Mavis, Alisha M. and et al.}, year={2023}, month={Oct} }
 @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={ABSTRACT 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{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={Abstract
                Background
                Epigenetic mechanisms are hypothesized to contribute substantially to the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, although empirical data are limited.
              
                Methods
                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.
              
                Results
                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).
              
                Conclusions
                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{skaar_dietze_alva-ornelas_ann_schones_hyslop_sistrunk_zalles_ambrose_kennedy_et al._2021, title={Epigenetic Dysregulation of KCNK9 Imprinting and Triple-Negative Breast Cancer}, volume={13}, ISSN={["2072-6694"]}, url={https://www.mdpi.com/2072-6694/13/23/6031}, DOI={10.3390/cancers13236031}, abstractNote={Genomic imprinting is an inherited form of parent-of-origin specific epigenetic gene regulation that is dysregulated by poor prenatal nutrition and environmental toxins. KCNK9 encodes for TASK3, a pH-regulated potassium channel membrane protein that is overexpressed in 40% of breast cancer. However, KCNK9 gene amplification accounts for increased expression in <10% of these breast cancers. Here, we showed that KCNK9 is imprinted in breast tissue and identified a differentially methylated region (DMR) controlling its imprint status. Hypomethylation at the DMR, coupled with biallelic expression of KCNK9, occurred in 63% of triple-negative breast cancers (TNBC). The association between hypomethylation and TNBC status was highly significant in African-Americans (p = 0.006), but not in Caucasians (p = 0.70). KCNK9 hypomethylation was also found in non-cancerous tissue from 77% of women at high-risk of developing breast cancer. Functional studies demonstrated that the KCNK9 gene product, TASK3, regulates mitochondrial membrane potential and apoptosis-sensitivity. In TNBC cells and non-cancerous mammary epithelial cells from high-risk women, hypomethylation of the KCNK9 DMR predicts for increased TASK3 expression and mitochondrial membrane potential (p < 0.001). This is the first identification of the KCNK9 DMR in mammary epithelial cells and demonstration that its hypomethylation in breast cancer is associated with increases in both mitochondrial membrane potential and apoptosis resistance. The high frequency of hypomethylation of the KCNK9 DMR in TNBC and non-cancerous breast tissue from high-risk women provides evidence that hypomethylation of the KNCK9 DMR/TASK3 overexpression may serve as a marker of risk and a target for prevention of TNBC, particularly in African American women.}, number={23}, journal={CANCERS}, author={Skaar, David A. and Dietze, Eric C. and Alva-Ornelas, Jackelyn A. and Ann, David and Schones, Dustin E. and Hyslop, Terry and Sistrunk, Christopher and Zalles, Carola and Ambrose, Adrian and Kennedy, Kendall and et al.}, year={2021}, month={Dec} }
 @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={SummaryBackgroundAlthough maternal systemic inflammation is hypothesized to link maternal pre‐pregnancy obesity to offspring metabolic dysfunction, patient empirical data are limited.ObjectivesIn this study, we hypothesized that pre‐pregnancy obesity alters systemic chemo/cytokines concentrations in pregnancy, and this alteration contributes to obesity in children.MethodsIn 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.ResultsAfter 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).ConclusionsData 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{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={ABSTRACT 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{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{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={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{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{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{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{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={Background: 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. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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. Citation: 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{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{cukier_skaar_rayner-evans_konidari_whitehead_jaworski_cuccaro_pericak-vance_gilbert_2009, title={Identification of chromosome 7 inversion breakpoints in an autistic family narrows candidate region for autism susceptibility}, volume={2}, ISSN={1939-3792 1939-3806}, url={http://dx.doi.org/10.1002/aur.96}, DOI={10.1002/aur.96}, abstractNote={AbstractChromosomal breaks and rearrangements have been observed in conjunction with autism and autistic spectrum disorders. A chromosomal inversion has been previously reported in autistic siblings, spanning the region from approximately 7q22.1 to 7q31. This family is distinguished by having multiple individuals with autism and associated disabilities. The region containing the inversion has been strongly implicated in autism by multiple linkage studies, and has been particularly associated with language defects in autism as well as in other disorders with language components. Mapping of the inversion breakpoints by FISH has localized the inversion to the region spanning approximately 99–108.75 Mb of chromosome 7. The proximal breakpoint has the potential to disrupt either the coding sequence or regulatory regions of a number of cytochrome P450 genes while the distal region falls in a relative gene desert. Copy number variant analysis of the breakpoint regions detected no duplication or deletion that could clearly be associated with disease status. Association analysis in our autism data set using single nucleotide polymorphisms located near the breakpoints showed no significant association with proximal breakpoint markers, but has identified markers near the distal breakpoint (∼108–110 Mb) with significant associations to autism. The chromosomal abnormality in this family strengthens the case for an autism susceptibility gene in the chromosome 7q22‐31 region and targets a candidate region for further investigation.}, number={5}, journal={Autism Research}, publisher={Wiley}, author={Cukier, Holly N. and Skaar, David A. and Rayner-Evans, Melissa Y. and Konidari, Ioanna and Whitehead, Patrice L. and Jaworski, James M. and Cuccaro, Michael L. and Pericak-Vance, Margaret A. and Gilbert, John R.}, year={2009}, month={Oct}, pages={258–266} }
 @article{skaar_shao_haines_stenger_jaworski_martin_delong_moore_mccauley_sutcliffe_et al._2005, title={Analysis of the RELN gene as a genetic risk factor for autism}, volume={10}, ISSN={1359-4184 1476-5578}, url={http://dx.doi.org/10.1038/sj.mp.4001614}, DOI={10.1038/sj.mp.4001614}, abstractNote={Several genome-wide screens have indicated the presence of an autism susceptibility locus within the distal long arm of chromosome 7 (7q). Mapping at 7q22 within this region is the candidate gene reelin (RELN). RELN encodes a signaling protein that plays a pivotal role in the migration of several neuronal cell types and in the development of neural connections. Given these neurodevelopmental functions, recent reports that RELN influences genetic risk for autism are of significant interest. The total data set consists of 218 Caucasian families collected by our group, 85 Caucasian families collected by AGRE, and 68 Caucasian families collected at Tufts University were tested for genetic association of RELN variants to autism. Markers included five single-nucleotide polymorphisms (SNPs) and a repeat in the 5′-untranslated region (5′-UTR). Tests for association in Duke and AGRE families were also performed on four additional SNPs in the genes PSMC2 and ORC5L, which flank RELN. Family-based association analyses (PDT, Geno-PDT, and FBAT) were used to test for association of single-locus markers and multilocus haplotypes with autism. The most significant association identified from this combined data set was for the 5′-UTR repeat (PDT P-value=0.002). These analyses show the potential of RELN as an important contributor to genetic risk in autism.}, number={6}, journal={Molecular Psychiatry}, publisher={Springer Science and Business Media LLC}, author={Skaar, D A and Shao, Y and Haines, J L and Stenger, J E and Jaworski, J and Martin, E R and DeLong, G R and Moore, J H and McCauley, J L and Sutcliffe, J S and et al.}, year={2005}, month={Jun}, pages={563–571} }