A genome-wide association study identifies IL23R as an inflammatory bowel disease gene

Richard H. Duerr, 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 Datta, Emily O. Kistner, L. Philip Schumm, Annette T. Lee, Peter K. Gregersen, M. Michael BarmadaJerome I. Rotter, Dan L. Nicolae, Judy H. Cho

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1461-1463
Number of pages3
JournalScience
Volume314
Issue number5804
DOIs
StatePublished - Dec 1 2006

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Genome-Wide Association Study
Inflammatory Bowel Diseases
Crohn Disease
Interleukin-23
Ulcerative Colitis
Genes
Cytokine Receptors
Abdominal Pain
Diarrhea
Chromosomes
Hemorrhage
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Duerr, R. H., Taylor, K. D., Brant, S. R., Rioux, J. D., Silverberg, M. S., Daly, M. J., ... Cho, J. H. (2006). A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science, 314(5804), 1461-1463. https://doi.org/10.1126/science.1135245

A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. / Duerr, Richard H.; Taylor, Kent D.; Brant, Steven R.; Rioux, John D.; Silverberg, Mark S.; Daly, Mark J.; Steinhart, A. Hillary; Abraham, Clara; Regueiro, Miguel; Griffiths, Anne; Dassopoulos, Themistocles; Bitton, Alain; Yang, Huiying; Targan, Stephan; Datta, Lisa; Kistner, Emily O.; Schumm, L. Philip; Lee, Annette T.; Gregersen, Peter K.; Barmada, M. Michael; Rotter, Jerome I.; Nicolae, Dan L.; Cho, Judy H.

In: Science, Vol. 314, No. 5804, 01.12.2006, p. 1461-1463.

Research output: Contribution to journalArticle

Duerr, RH, Taylor, KD, Brant, SR, Rioux, JD, Silverberg, MS, Daly, MJ, Steinhart, AH, Abraham, C, Regueiro, M, Griffiths, A, Dassopoulos, T, Bitton, A, Yang, H, Targan, S, Datta, L, Kistner, EO, Schumm, LP, Lee, AT, Gregersen, PK, Barmada, MM, Rotter, JI, Nicolae, DL & Cho, JH 2006, 'A genome-wide association study identifies IL23R as an inflammatory bowel disease gene', Science, vol. 314, no. 5804, pp. 1461-1463. https://doi.org/10.1126/science.1135245
Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006 Dec 1;314(5804):1461-1463. https://doi.org/10.1126/science.1135245
Duerr, Richard H. ; Taylor, Kent D. ; Brant, Steven R. ; Rioux, John D. ; Silverberg, Mark S. ; Daly, Mark J. ; Steinhart, A. Hillary ; Abraham, Clara ; Regueiro, Miguel ; Griffiths, Anne ; Dassopoulos, Themistocles ; Bitton, Alain ; Yang, Huiying ; Targan, Stephan ; Datta, Lisa ; Kistner, Emily O. ; Schumm, L. Philip ; Lee, Annette T. ; Gregersen, Peter K. ; Barmada, M. Michael ; Rotter, Jerome I. ; Nicolae, Dan L. ; Cho, Judy H. / A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. In: Science. 2006 ; Vol. 314, No. 5804. pp. 1461-1463.
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AU - Gregersen, Peter K.

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AU - Cho, Judy H.

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