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MYH9 is associated with nondiabetic end-stage renal disease in African Americans. 2008
W H Linda Kao, and
Michael J Klag, and
Lucy A Meoni, and
David Reich, and
Yvette Berthier-Schaad, and
Man Li, and
Josef Coresh, and
Nick Patterson, and
Arti Tandon, and
Neil R Powe, and
Nancy E Fink, and
John H Sadler, and
Matthew R Weir, and
Hanna E Abboud, and
Sharon G Adler, and
Jasmin Divers, and
Sudha K Iyengar, and
Barry I Freedman, and
Paul L Kimmel, and
William C Knowler, and
Orly F Kohn, and
Kristopher Kramp, and
David J Leehey, and
Susanne B Nicholas, and
Madeleine V Pahl, and
Jeffrey R Schelling, and
John R Sedor, and
Denyse Thornley-Brown, and
Cheryl A Winkler, and
Michael W Smith, and
Rulan S Parekh, and
Department of Epidemiology, School of Medicine and Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21287, USA. wkao@jhsph.edu
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.
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