MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-10

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

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. More... »

PAGES

1175-1184

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.226

    DOI

    http://dx.doi.org/10.1038/ng.226

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1022042808

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/18794856


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