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

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

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

Author(s) -

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 M. Griffiths,

Themistocles Dassopoulos,

Alain Bitton,

Huiying Yang,

Stephan R. Targan,

Lisa W. 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

Publication year - 2006

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.1135245

Subject(s) - inflammatory bowel disease , disease , genome wide association study , gene , genome , genetics , genetic association , biology , medicine , genotype , single nucleotide polymorphism

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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