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 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

doi:10.1126/science.1135245

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

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2290 Scopus citations

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 language	English (US)
Pages (from-to)	1461-1463
Number of pages	3
Journal	Science
Volume	314
Issue number	5804
DOIs	https://doi.org/10.1126/science.1135245
State	Published - Dec 1 2006
Externally published	Yes

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Duerr, R. H., Taylor, K. D., Brant, S. R., Rioux, J. D., Silverberg, M. S., Daly, M. J., Steinhart, A. H., Abraham, C., Regueiro, M., Griffiths, A., Dassopoulos, T., Bitton, A., Yang, H., Targan, S., Datta, L. W., Kistner, E. O., Schumm, L. P., Lee, A. T., Gregersen, P. K., ... 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

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, LW, 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

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title = "A genome-wide association study identifies IL23R as an inflammatory bowel disease gene",

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.",

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

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AU - Silverberg, Mark S.

AU - Daly, Mark J.

AU - Steinhart, A. Hillary

AU - Abraham, Clara

AU - Regueiro, Miguel

AU - Griffiths, Anne

AU - Dassopoulos, Themistocles

AU - Bitton, Alain

AU - Yang, Huiying

AU - Targan, Stephan

AU - Datta, Lisa Wu

AU - Kistner, Emily O.

AU - Schumm, L. Philip

AU - Lee, Annette T.

AU - Gregersen, Peter K.

AU - Barmada, M. Michael

AU - Rotter, Jerome I.

AU - Nicolae, Dan L.

AU - Cho, Judy H.

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

Abstract

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