MYH9 is a Major-effect Risk Gene for Focal Segmental Glomerulosclerosis

Overview

Journal Nat Genet

Specialty Genetics

Date 2008 Sep 17

PMID 18794856

Citations 381

Authors

Jeffrey B Kopp

Michael W Smith

George W Nelson

Randall C Johnson

Barry I Freedman

Donald W Bowden

Taras Oleksyk

Louise M McKenzie

Hiroshi Kajiyama

Tejinder S Ahuja

Jeffrey S Berns

William Briggs

Monique E Cho

Richard A Dart

Paul L Kimmel

Stephen M Korbet

Donna M Michel

Michele H Mokrzycki

Jeffrey R Schelling

Eric Simon

Howard Trachtman

David Vlahov

Cheryl A Winkler

Affiliations

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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.

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