2. Academic Validation
  3. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene

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.
Richard H Duerr 1,  Kent D Taylor,  Steven R Brant,  John D Rioux,  Mark S Silverberg,  Mark J Daly,  A Hillary Steinhart,  Clara Abraham,  Miguel Regueiro,  Anne Griffiths,  Themistocles Dassopoulos,  Alain Bitton,  Huiying Yang,  Stephan Targan,  Lisa Wu Datta,  Emily O Kistner,  L Philip Schumm,  Annette T Lee,  Peter K Gregersen,  M Michael Barmada,  Jerome I Rotter,  Dan L Nicolae,  Judy H Cho
Affiliations

Affiliation

  • 1 Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, University of Pittsburgh Medical Center Presbyterian, Mezzanine Level, C-Wing, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
PMID: 17068223 DOI: 10.1126/science.1135245
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.

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