Identification of new susceptibility loci for IgA nephropathy in Han Chinese

Nat Commun. 2015 Jun 1:6:7270. doi: 10.1038/ncomms8270.

Abstract

IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. Previously identified genome-wide association study (GWAS) loci explain only a fraction of disease risk. To identify novel susceptibility loci in Han Chinese, we conduct a four-stage GWAS comprising 8,313 cases and 19,680 controls. Here, we show novel associations at ST6GAL1 on 3q27.3 (rs7634389, odds ratio (OR)=1.13, P=7.27 × 10(-10)), ACCS on 11p11.2 (rs2074038, OR=1.14, P=3.93 × 10(-9)) and ODF1-KLF10 on 8q22.3 (rs2033562, OR=1.13, P=1.41 × 10(-9)), validate a recently reported association at ITGAX-ITGAM on 16p11.2 (rs7190997, OR=1.22, P=2.26 × 10(-19)), and identify three independent signals within the DEFA locus (rs2738058, P=1.15 × 10(-19); rs12716641, P=9.53 × 10(-9); rs9314614, P=4.25 × 10(-9), multivariate association). The risk variants on 3q27.3 and 11p11.2 show strong association with mRNA expression levels in blood cells while allele frequencies of the risk variants within ST6GAL1, ACCS and DEFA correlate with geographical variation in IgAN prevalence. Our findings expand our understanding on IgAN genetic susceptibility and provide novel biological insights into molecular mechanisms underlying IgAN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / genetics
  • Asian People / genetics*
  • CD11b Antigen / genetics
  • CD11c Antigen / genetics
  • Case-Control Studies
  • China
  • DEFICIENS Protein / genetics
  • Early Growth Response Transcription Factors / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Glomerulonephritis, IGA / genetics*
  • Heat-Shock Proteins / genetics
  • Humans
  • Kruppel-Like Transcription Factors / genetics
  • Lyases / genetics
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Sialyltransferases / genetics
  • Young Adult

Substances

  • Antigens, CD
  • CD11b Antigen
  • CD11c Antigen
  • DEFICIENS Protein
  • Early Growth Response Transcription Factors
  • Heat-Shock Proteins
  • ITGAM protein, human
  • KLF10 protein, human
  • Kruppel-Like Transcription Factors
  • ODF1 protein, human
  • Sialyltransferases
  • ST6GAL1 protein, human
  • Lyases
  • 1-aminocyclopropanecarboxylate synthase