A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy

Nat Genet. 2011 Dec 25;44(2):178-82. doi: 10.1038/ng.1047.

Abstract

We performed a two-stage genome-wide association study of IgA nephropathy (IgAN) in Han Chinese, with 1,434 affected individuals (cases) and 4,270 controls in the discovery phase and follow-up of the top 61 SNPs in an additional 2,703 cases and 3,464 controls. We identified associations at 17p13 (rs3803800, P = 9.40 × 10(-11), OR = 1.21; rs4227, P = 4.31 × 10(-10), OR = 1.23) and 8p23 (rs2738048, P = 3.18 × 10(-14), OR = 0.79) that implicated the genes encoding tumor necrosis factor (TNFSF13) and α-defensin (DEFA) as susceptibility genes. In addition, we found multiple associations in the major histocompatibility complex (MHC) region (rs660895, P = 4.13 × 10(-20), OR = 1.34; rs1794275, P = 3.43 × 10(-13), OR = 1.30; rs2523946, P = 1.74 × 10(-11), OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 × 10(-11), OR = 0.78). We also found that rs660895 was associated with clinical subtypes of IgAN (P = 0.003), proteinuria (P = 0.025) and IgA levels (P = 0.047). Our findings show that IgAN is associated with variants near genes involved in innate immunity and inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian Continental Ancestry Group / genetics*
  • Asian Continental Ancestry Group / statistics & numerical data
  • Case-Control Studies
  • Female
  • Genetic Loci*
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study*
  • Glomerulonephritis, IGA / diagnosis
  • Glomerulonephritis, IGA / epidemiology
  • Glomerulonephritis, IGA / genetics*
  • Humans
  • Immunoglobulin A / blood
  • Major Histocompatibility Complex / genetics
  • Male
  • Polymorphism, Single Nucleotide
  • Proteinuria / genetics
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / genetics
  • alpha-Defensins / genetics

Substances

  • Immunoglobulin A
  • TNFSF13 protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • alpha-Defensins