A genome-wide association study identifies IL23R as an inflammatory bowel disease gene.
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.
Duerr
Richard H
RH
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.
Taylor
Kent D
KD
Brant
Steven R
SR
Rioux
John D
JD
Silverberg
Mark S
MS
Daly
Mark J
MJ
Steinhart
A Hillary
AH
Abraham
Clara
C
Regueiro
Miguel
M
Griffiths
Anne
A
Dassopoulos
Themistocles
T
Bitton
Alain
A
Yang
Huiying
H
Targan
Stephan
S
Datta
Lisa Wu
LW
Kistner
Emily O
EO
Schumm
L Philip
LP
Lee
Annette T
AT
Gregersen
Peter K
PK
Barmada
M Michael
MM
Rotter
Jerome I
JI
Nicolae
Dan L
DL
Cho
Judy H
JH
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
D005819:Genetic Markers; C515500:IL23R protein, human; D053759:Interleukin-23; D018123:Receptors, Interleukin