Genome-wide association study identifies susceptibility loci for IgA nephropathy

Nat Genet. 2011 Mar 13;43(4):321-7. doi: 10.1038/ng.787.

Abstract

We carried out a genome-wide association study of IgA nephropathy, a major cause of kidney failure worldwide. We studied 1,194 cases and 902 controls of Chinese Han ancestry, with targeted follow up in Chinese and European cohorts comprising 1,950 cases and 1,920 controls. We identified three independent loci in the major histocompatibility complex, as well as a common deletion of CFHR1 and CFHR3 at chromosome 1q32 and a locus at chromosome 22q12 that each surpassed genome-wide significance (P values for association between 1.59 × 10⁻²⁶ and 4.84 × 10⁻⁹ and minor allele odds ratios of 0.63-0.80). These five loci explain 4-7% of the disease variance and up to a tenfold variation in interindividual risk. Many of the alleles that protect against IgA nephropathy impart increased risk for other autoimmune or infectious diseases, and IgA nephropathy risk allele frequencies closely parallel the variation in disease prevalence among Asian, European and African populations, suggesting complex selective pressures.

Publication types

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

MeSH terms

  • Adult
  • Alleles
  • Asian Continental Ancestry Group / genetics
  • Blood Proteins / genetics
  • Case-Control Studies
  • Chromosomes, Human, Pair 1 / genetics
  • Chromosomes, Human, Pair 22 / genetics
  • Cohort Studies
  • Complement C3b Inactivator Proteins / genetics
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Glomerulonephritis, IGA / genetics*
  • Glomerulonephritis, IGA / immunology
  • HLA Antigens / genetics
  • Humans
  • Major Histocompatibility Complex
  • Male
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Selection, Genetic
  • Young Adult

Substances

  • Blood Proteins
  • CFHR1 protein, human
  • CFHR3 protein, human
  • Complement C3b Inactivator Proteins
  • HLA Antigens