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- Title
MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis.
- Authors
Kopp, Jeffrey B; Smith, Michael W; Nelson, George W; Johnson, Randall C; Freedman, Barry I; Bowden, Donald W; Oleksyk, Taras; McKenzie, Louise M; Kajiyama, Hiroshi; Ahuja, Tejinder S; Berns, Jeffrey S; Briggs, William; Cho, Monique E; Dart, Richard A; Kimmel, Paul L; Korbet, Stephen M; Michel, Donna M; Mokrzycki, Michele H; Schelling, Jeffrey R; Simon, Eric; Trachtman, Howard; Vlahov, David; Winkler, Cheryl A
- Abstract
The increased burden of chronic kidney and end-stage kidney diseases (ESKD) in populations of African ancestry has been largely unexplained. To identify genetic variants predisposing to idiopathic and HIV-1-associated focal segmental glomerulosclerosis (FSGS), we carried out an admixture-mapping linkage-disequilibrium genome scan on 190 African American individuals with FSGS and 222 controls. We identified a chromosome 22 region with a genome-wide logarithm of the odds (lod) score of 9.2 and a peak lod of 12.4 centered on MYH9, a functional candidate gene expressed in kidney podocytes. Multiple MYH9 SNPs and haplotypes were recessively associated with FSGS, most strongly a haplotype spanning exons 14 through 23 (OR = 5.0, 95% CI = 3.5-7.1; P = 4 x 10(-23), n = 852). This association extended to hypertensive ESKD (OR = 2.2, 95% CI = 1.5-3.4; n = 433), but not type 2 diabetic ESKD (n = 476). Genetic variation at the MYH9 locus substantially explains the increased burden of FSGS and hypertensive ESKD among African Americans.
- Publication
Nature genetics, 2008, Vol 40, Issue 10, p1175
- ISSN
1546-1718
- Publication type
Journal Article
- DOI
10.1038/ng.226