MYH9 is associated with nondiabetic end-stage renal disease in African Americans

W. H.Linda Kao, Michael J. Klag, Lucy A. Meoni, David Reich, Yvette Berthier-Schaad, Man Li, Josef Coresh, Nick Patterson, Arti Tandon, Neil R. Powe, Nancy E. Fink, John H. Sadler, Matthew R. Weir, Hanna E. Abboud, Sharon G. Adler, Jasmin Divers, Sudha K. Iyengar, Barry I. Freedman, Paul L. Kimmel, William C. KnowlerOrly F. Kohn, Kristopher Kramp, David J. Leehey, Susanne B. Nicholas, Madeleine V. Pahl, Jeffrey R. Schelling, John R. Sedor, Denyse Thornley-Brown, Cheryl A. Winkler, Michael W. Smith, Rulan S. Parekh

Research output: Contribution to journalArticlepeer-review

498 Scopus citations

Abstract

As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant association between excess African ancestry and nondiabetic ESRD (lod score = 5.70) but not diabetic ESRD (lod = 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% CI = 0.39-0.63) compared to African ancestry. Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans.

Original languageEnglish (US)
Pages (from-to)1185-1192
Number of pages8
JournalNature Genetics
Volume40
Issue number10
DOIs
StatePublished - Oct 1 2008

ASJC Scopus subject areas

  • Genetics

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