A Genome-Wide Association Study Identifies IL23R as an Inflammatory Bowel Disease Gene

Science. 2006 Dec 1;314(5804):1461-3. doi: 10.1126/science.1135245. Epub 2006 Oct 26.

Abstract

The inflammatory bowel diseases Crohn's disease and ulcerative colitis are common, chronic disorders that cause abdominal pain, diarrhea, and gastrointestinal bleeding. To identify genetic factors that might contribute to these disorders, we performed a genome-wide association study. We found a highly significant association between Crohn's disease and the IL23R gene on chromosome 1p31, which encodes a subunit of the receptor for the proinflammatory cytokine interleukin-23. An uncommon coding variant (rs11209026, c.1142G>A, p.Arg381Gln) confers strong protection against Crohn's disease, and additional noncoding IL23R variants are independently associated. Replication studies confirmed IL23R associations in independent cohorts of patients with Crohn's disease or ulcerative colitis. These results and previous studies on the proinflammatory role of IL-23 prioritize this signaling pathway as a therapeutic target in inflammatory bowel disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Case-Control Studies
  • Chromosomes, Human, Pair 1 / genetics
  • Cohort Studies
  • Colitis, Ulcerative / genetics
  • Crohn Disease / genetics*
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Genome, Human
  • Haplotypes
  • Humans
  • Interleukin-23 / metabolism
  • Jews / genetics
  • Linkage Disequilibrium
  • Polymorphism, Single Nucleotide*
  • Receptors, Interleukin / genetics*
  • Receptors, Interleukin / physiology
  • Signal Transduction

Substances

  • Genetic Markers
  • IL23R protein, human
  • Interleukin-23
  • Receptors, Interleukin

Associated data

  • RefSeq/NM_144701