@article{c2a0c1751d5a4850abe23c374ec0a336,
title = "Genetic association and gene-gene interaction analyses in African American dialysis patients with nondiabetic nephropathy",
abstract = "Background: African Americans have increased susceptibility to nondiabetic nephropathy relative to European Americans. Study Design: Follow-up of a pooled genome-wide association study (GWAS) in African American dialysis patients with nondiabetic nephropathy; novel gene-gene interaction analyses. Setting & Participants: Wake Forest sample: 962 African American nondiabetic nephropathy cases, 931 non-nephropathy controls. Replication sample: 668 Family Investigation of Nephropathy and Diabetes (FIND) African American nondiabetic nephropathy cases, 804 non-nephropathy controls. Predictors: Individual genotyping of top 1,420 pooled GWAS-associated single-nucleotide polymorphisms (SNPs) and 54 SNPs in 6 nephropathy susceptibility genes. Outcomes: APOL1 genetic association and additional candidate susceptibility loci interacting with or independently from APOL1. Results: The strongest GWAS associations included 2 noncoding APOL1 SNPs, rs2239785 (OR, 0.33; dominant; P = 5.9 × 10 -24) and rs136148 (OR, 0.54; additive; P = 1.1 × 10 -7) with replication in FIND (P = 5.0 × 10 -21 and 1.9 × 10 -05, respectively). rs2239785 remained associated significantly after controlling for the APOL1 G1 and G2 coding variants. Additional top hits included a CFH SNP (OR from meta-analysis in the 3,367 African American cases and controls, 0.81; additive; P = 6.8 × 10 -4). The 1,420 SNPs were tested for interaction with APOL1 G1 and G2 variants. Several interactive SNPs were detected; the most significant was rs16854341 in the podocin gene (NPHS2; P = 0.0001). Limitations: Nonpooled GWASs have not been performed in African American patients with nondiabetic nephropathy. Conclusions: This follow-up of a pooled GWAS provides additional and independent evidence that APOL1 variants contribute to nondiabetic nephropathy in African Americans and identified additional associated and interactive nondiabetic nephropathy susceptibility genes.",
keywords = "APOL1, African American, CFH, Family Investigation of Nephropathy and Diabetes (FIND), end-stage renal disease, focal segmental glomerulosclerosis (FSGS), hypertension",
author = "Bostrom, {Meredith A.} and Kao, {W. H.Linda} and Man Li and Abboud, {Hanna E.} and Adler, {Sharon G.} and Iyengar, {Sudha K.} and Kimmel, {Paul L.} and Hanson, {Robert L.} and Nicholas, {Susanne B.} and Rasooly, {Rebekah S.} and Sedor, {John R.} and Josef Coresh and Kohn, {Orly F.} and Leehey, {David J.} and Denyse Thornley-Brown and Bottinger, {Erwin P.} and Lipkowitz, {Michael S.} and Meoni, {Lucy A.} and Klag, {Michael J.} and Lingyi Lu and Hicks, {Pamela J.} and Langefeld, {Carl D.} and Parekh, {Rulan S.} and Bowden, {Donald W.} and Freedman, {Barry I.}",
note = "Funding Information: Support: This study was supported in part by National Institutes of Health (NIH) grants R01 DK 070941 and R01 DK 084149 (Dr Freedman) and R01 DK53591 (Dr Bowden). Dr Bostrom was supported by F32 DK080617 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Computing resources were provided by the Wake Forest University Health Sciences Center for Public Health Genomics. This study was also supported by FIND grants U01DK57292 , U01DK57329 , U01DK057300 , U01DK057298 , U01DK057249 , U01DK57295 , U01DK070657 , U01DK057303 , U01DK070657 , U01DK57304 and CHOICE study DK07024 from the NIDDK and in part by the Intramural Research Program of the NIDDK. This project has been funded in whole or in part with federal funds from the NIH National Cancer Institute (NCI) under contract N01-CO-12400 and the Intramural Research Program of the NIH-NCI Center for Cancer Research. This work also was supported by the National Center for Research Resources for the General Clinical Research Center grants: Case Western Reserve University , M01-RR-000080 ; Wake Forest University , M01-RR-07122 ; Harbor–University of California, Los Angeles Medical Center , M01-RR-00425 ; College of Medicine, University of California , Irvine, M01-RR-00827-29 ; University of New Mexico , HSC M01-RR-00997 ; and Frederic C. Bartter , M01-RR-01346 . The CHOICE Study was supported in part by HS08365 from the Agency for Healthcare Research and Quality , Rockville, MD, and HL62985 from the National Heart, Lung, and Blood Institute , Bethesda, MD. Genotyping was performed by the Center for Inherited Disease Research, which is fully funded through a federal contract from the NIH to Johns Hopkins University ( N01-HG-65403 ). ",
year = "2012",
month = feb,
doi = "10.1053/j.ajkd.2011.09.020",
language = "English (US)",
volume = "59",
pages = "210--221",
journal = "American Journal of Kidney Diseases",
issn = "0272-6386",
publisher = "W.B. Saunders Ltd",
number = "2",
}