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.
authors.affiliation: 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.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Duerr
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.forename: Steven R
authors.initials: SR
authors.lastname: Brant
authors.forename: John D
authors.initials: JD
authors.lastname: Rioux
authors.forename: Mark S
authors.initials: MS
authors.lastname: Silverberg
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Daly
authors.forename: A Hillary
authors.initials: AH
authors.lastname: Steinhart
authors.forename: Clara
authors.initials: C
authors.lastname: Abraham
authors.forename: Miguel
authors.initials: M
authors.lastname: Regueiro
authors.forename: Anne
authors.initials: A
authors.lastname: Griffiths
authors.forename: Themistocles
authors.initials: T
authors.lastname: Dassopoulos
authors.forename: Alain
authors.initials: A
authors.lastname: Bitton
authors.forename: Huiying
authors.initials: H
authors.lastname: Yang
authors.forename: Stephan
authors.initials: S
authors.lastname: Targan
authors.forename: Lisa Wu
authors.initials: LW
authors.lastname: Datta
authors.forename: Emily O
authors.initials: EO
authors.lastname: Kistner
authors.forename: L Philip
authors.initials: LP
authors.lastname: Schumm
authors.forename: Annette T
authors.initials: AT
authors.lastname: Lee
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.forename: M Michael
authors.initials: MM
authors.lastname: Barmada
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Dan L
authors.initials: DL
authors.lastname: Nicolae
authors.forename: Judy H
authors.initials: JH
authors.lastname: Cho
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D015894:Genome, Human; D006239:Haplotypes; D006801:Humans; D053759:Interleukin-23 / Q000378:metabolism; D007585:Jews / Q000235:genetics; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction
chemical_list: D005819:Genetic Markers; C515500:IL23R protein, human; D053759:Interleukin-23; D018123:Receptors, Interleukin