Title: Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility
Authors: Franke, Andre ×
Balschun, Tobias
Karlsen, Tom H
Sventoraityte, Jurgita
Nikolaus, Susanna
Mayr, Gabriele
Domingues, Francisco S
Albrecht, Mario
Nothnagel, Michael
Ellinghaus, David
Sina, Christian
Onnie, Clive M
Weersma, Rinse K
Stokkers, Pieter C. F
Wijmenga, Cisca
Gazouli, Maria
Strachan, David
McArdle, Wendy L
Vermeire, Severine
Rutgeerts, Paul
Rosenstiel, Philip
Krawczak, Michael
Vatn, Morten H
Mathew, Christopher G
Schreiber, Stefan #
Issue Date: Nov-2008
Publisher: Nature Publishing Group
Series Title: Nature Genetics vol:40 issue:11 pages:1319-1323
Abstract: Inflammatory bowel disease (IBD) typically manifests as either ulcerative colitis (UC) or Crohn's disease (CD). Systematic identification of susceptibility genes for IBD has thus far focused mainly on CD, and little is known about the genetic architecture of UC. Here we report a genome-wide association study with 440,794 SNPs genotyped in 1,167 individuals with UC and 777 healthy controls. Twenty of the most significantly associated SNPs were tested for replication in three independent European case-control panels comprising a total of 1,855 individuals with UC and 3,091 controls. Among the four consistently replicated markers, SNP rs3024505 immediately flanking the IL10 (interleukin 10) gene on chromosome 1q32.1 showed the most significant association in the combined verification samples (P = 1.35 x 10(-12); OR = 1.46 (1.31-1.62)). The other markers were located in ARPC2 and in the HLA-BTNL2 region. Association between rs3024505 and CD (1,848 cases, 1,804 controls) was weak (P = 0.013; OR = 1.17 (1.01-1.34)). IL10 is an immunosuppressive cytokine that has long been proposed to influence IBD pathophysiology. Our findings strongly suggest that defective IL10 function is central to the pathogenesis of the UC subtype of IBD.
ISSN: 1061-4036
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Research in GastroIntestinal Disorders
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science