@article{stafford-smith_podgoreanu_swaminathan_phillips-bute_mathew_hauser_winn_milano_nielsen_smith_et al._2005, title={Association of genetic polymorphisms with risk of renal injury after coronary bypass graft surgery}, volume={45}, ISSN={0272-6386}, url={http://dx.doi.org/10.1053/j.ajkd.2004.11.021}, DOI={10.1053/j.ajkd.2004.11.021}, abstractNote={BACKGROUND
Post-cardiac surgery renal dysfunction is a common, serious, multifactorial disorder, with interpatient variability predicted poorly by preoperative clinical, procedural, and biological markers. Therefore, we tested the hypothesis that selected gene variants are associated with acute renal injury, reflected by a serum creatinine level increase after cardiac surgery.


METHODS
One thousand six hundred seventy-one patients undergoing aortocoronary surgery were studied. Clinical covariates were recorded. DNA was isolated from preoperative blood; mass spectrometry was used for genotype analysis. A model was developed relating clinical and genetic factors to postoperative acute renal injury.


RESULTS
A race effect was found; therefore, Caucasians and African Americans were analyzed separately. Overall, clinical factors alone account poorly for postoperative renal injury, although more so in African Americans than Caucasians. When 12 candidate polymorphisms were assessed, 2 alleles (interleukin 6 -572C and angiotensinogen 842C) showed a strong association with renal injury in Caucasians (P < 0.0001; >50% decrease in renal filtration when they present together). Using less stringent criteria for significance (0.01 > P > 0.001), 4 additional polymorphisms are identified (apolipoproteinE 448C [4], angiotensin receptor1 1166C, and endothelial nitric oxide synthase [eNOS] 894T in Caucasians; eNOS 894T and angiotensin-converting enzyme deletion and insertion in African Americans). Adding genetic to clinical factors resulted in the best model, with overall ability to explain renal injury increasing approximately 4-fold in Caucasians and doubling in African Americans (P < 0.0005).


CONCLUSION
In this study, we identify genetic polymorphisms that collectively provide 2- to 4-fold improvement over preoperative clinical factors alone in explaining post-cardiac surgery renal dysfunction. From a mechanistic perspective, most identified genetic variants are associated with increased renal inflammatory and/or vasoconstrictor responses.}, number={3}, journal={American Journal of Kidney Diseases}, publisher={Elsevier BV}, author={Stafford-Smith, Mark and Podgoreanu, Mihai and Swaminathan, Madhav and Phillips-Bute, Barbara and Mathew, Joseph P. and Hauser, Elizabeth H. and Winn, Michelle P. and Milano, Carmelo and Nielsen, Dahlia M. and Smith, Mike and et al.}, year={2005}, month={Mar}, pages={519–530} }
 @article{kaplan_morris_2001, title={Issues concerning association studies for fine mapping a susceptibility gene for a complex disease}, volume={20}, ISSN={["0741-0395"]}, DOI={10.1002/gepi.1012}, abstractNote={AbstractThe usefulness of association studies for fine mapping loci with common susceptibility alleles for complex genetic diseases in outbred populations is unclear. We investigate this issue for a battery of tightly linked anonymous genetic markers spanning a candidate region centered around a disease locus, and study the joint behavior of chi‐square statistics used to discover and to localize the disease locus. We used simulation methods based on a coalescent process with mutation, recombination, and genetic drift to examine the spatial distribution of markers with large noncentrality parameters in a case‐control study design. Simulations with a disease allele at intermediate frequency, presumably representing an old mutation, tend to exhibit the largest noncentrality parameter values at markers near the disease locus. In contrast, simulations with a disease allele at low frequency, presumably representing a young mutation, often exhibit the largest noncentrality parameter values at markers scattered over the candidate region. In the former cases, sample sizes or marker densities sufficient to detect association are likely to lead to useful localization, whereas, in the latter case, localization of the disease locus within the candidate region is much less likely, regardless of the sample size or density of the map. The effects of increasing sample size or marker density are also investigated. Based upon a single marker analysis, we find that a simple strategy of choosing the marker with the smallest associated P value to begin a laboratory search for the disease locus performs adequately for a common disease allele. We also investigated a strategy of pooling nearby sites to form multiple allele markers. Using multiple degree of freedom chi‐square tests for two or three nearby sites, we found no clear advantage of this form of pooling over a single marker analysis. Genet. Epidemiol. 20:432–457, 2001. Published by Wiley‐Liss, 2001.}, number={4}, journal={GENETIC EPIDEMIOLOGY}, author={Kaplan, N and Morris, R}, year={2001}, month={May}, pages={432–457} }
 @article{sidik_morris_1999, title={Nonparametric step-down test procedures for finding minimum effective dose}, volume={9}, number={2}, journal={Journal of Biopharmaceutical Statistics}, author={Sidik, K. and Morris, R. W.}, year={1999}, pages={217–240} }