A Genome-Wide Association Study Identifies IL23R as an Inflammatory Bowel Disease Gene-Reference-Cited by-同舟云学术

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

Published:2006-12 Issue:5804 Volume:314 Page:1461-1463
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Duerr Richard H.¹²³⁴⁵,Taylor Kent D.¹²³⁴⁵,Brant Steven R.¹²³⁴⁵,Rioux John D.¹²³⁴⁵,Silverberg Mark S.¹²³⁴⁵,Daly Mark J.¹²³⁴⁵,Steinhart A. Hillary¹²³⁴⁵,Abraham Clara¹²³⁴⁵,Regueiro Miguel¹²³⁴⁵,Griffiths Anne¹²³⁴⁵,Dassopoulos Themistocles¹²³⁴⁵,Bitton Alain¹²³⁴⁵,Yang Huiying¹²³⁴⁵,Targan Stephan¹²³⁴⁵,Datta Lisa Wu¹²³⁴⁵,Kistner Emily O.¹²³⁴⁵,Schumm L. Philip¹²³⁴⁵,Lee Annette T.¹²³⁴⁵,Gregersen Peter K.¹²³⁴⁵,Barmada M. Michael¹²³⁴⁵,Rotter Jerome I.¹²³⁴⁵,Nicolae Dan L.¹²³⁴⁵,Cho Judy H.¹²³⁴⁵

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.

2. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Crabtree A300, 130 Desoto Street, Pittsburgh, PA15261, USA.

3. Medical Genetics Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.

4. IBD Center, Division of Gastroenterology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.

5. Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, Johns Hopkins University School of Medicine, B136, 1503 East Jefferson Street, Baltimore, MD 21231, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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