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

Nat Genet. 2008 Oct;40(10):1185-92. doi: 10.1038/ng.232. Epub 2008 Sep 14.

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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • African Americans / genetics
  • Case-Control Studies
  • Chromosome Mapping
  • Chromosomes, Human, Pair 22 / genetics*
  • Cohort Studies
  • DNA Primers / chemistry
  • Diabetes Mellitus / genetics*
  • Diabetes Mellitus / pathology
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Linkage
  • Genetic Predisposition to Disease / genetics*
  • Genome, Human
  • Glomerulosclerosis, Focal Segmental / genetics
  • Glomerulosclerosis, Focal Segmental / pathology
  • Haplotypes / genetics*
  • Humans
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / pathology
  • Lod Score
  • Male
  • Middle Aged
  • Molecular Motor Proteins / genetics*
  • Myosin Heavy Chains / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Prospective Studies
  • Risk Factors

Substances

  • DNA Primers
  • MYH9 protein, human
  • Molecular Motor Proteins
  • Myosin Heavy Chains

Grant support