A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population

Nat Genet. 2009 Dec;41(12):1325-9. doi: 10.1038/ng.482. Epub 2009 Nov 15.


Ulcerative colitis is one of the principal forms of inflammatory bowel disease with complex manifestations. Although previous studies have indicated that there is a genetic contribution to the pathogenesis of ulcerative colitis, the genes influencing susceptibility to the disease have not been fully determined. To identify genetic factors conferring risk of ulcerative colitis, here we conducted a two-stage genome-wide association study and subsequent replication study using 1,384 Japanese individuals with ulcerative colitis and 3,057 control subjects. In addition to the expected strong association with the major histocompatibility complex (MHC) region, we identified three new susceptibility loci: the immunoglobulin receptor gene FCGR2A (rs1801274, P = 1.56 x 10(-12)), a locus on chromosome 13q12 (rs17085007, P = 6.64 x 10(-8)) and the glycoprotein gene SLC26A3 (rs2108225, P = 9.50 x 10(-8)). rs1801274 is a nonsynonymous SNP of FCGR2A that is reported to have a critical effect on receptor binding affinity for IgG and to be associated with other autoimmune diseases. Our findings provide insight into the molecular pathogenesis of ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiporters / genetics
  • Asian People / genetics
  • Chloride-Bicarbonate Antiporters
  • Chromosomes, Human, Pair 13 / genetics
  • Colitis, Ulcerative / epidemiology
  • Colitis, Ulcerative / genetics*
  • Colitis, Ulcerative / pathology
  • Disease Susceptibility / epidemiology
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Japan
  • Major Histocompatibility Complex / genetics
  • Polymorphism, Single Nucleotide
  • Population Groups
  • Receptors, IgG / genetics
  • Sulfate Transporters


  • Antiporters
  • Chloride-Bicarbonate Antiporters
  • FCGR2A protein, human
  • Receptors, IgG
  • SLC26A3 protein, human
  • Sulfate Transporters