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

Nat Genet. 2008 Oct;40(10):1175-84. doi: 10.1038/ng.226. Epub 2008 Sep 14.

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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • AIDS-Associated Nephropathy / genetics
  • Adult
  • African Americans / genetics*
  • Case-Control Studies
  • Chromosome Mapping
  • Chromosomes, Human, Pair 22 / genetics*
  • DNA Primers / chemistry
  • 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
  • Hypertension / genetics
  • Lod Score
  • Male
  • Middle Aged
  • Molecular Motor Proteins / genetics*
  • Myosin Heavy Chains / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors

Substances

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