TY - JOUR
T1 - High-density mapping of the MHC identifies a shared role for HLA-DRB1∗01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis
AU - Australia and New Zealand IBDGC
AU - Belgium IBD Genetics Consortium
AU - Italian Group for IBD Genetic Consortium
AU - NIDDK Inflammatory Bowel Disease Genetics Consortium
AU - United Kingdom IBDGC
AU - Wwellcome Trust Case Control Consortium &Quebec IBD Genetics Consortium
AU - Goyette, Philippe
AU - Boucher, Gabrielle
AU - Mallon, Dermot
AU - Ellinghaus, Eva
AU - Jostins, Luke
AU - Huang, Hailiang
AU - Ripke, Stephan
AU - Gusareva, Elena S.
AU - Annese, Vito
AU - Hauser, Stephen L.
AU - Oksenberg, Jorge R.
AU - Thomsen, Ingo
AU - Leslie, Stephen
AU - Daly, Mark J.
AU - Van Steen, Kristel
AU - Duerr, Richard H.
AU - Barrett, Jeffrey C.
AU - McGovern, Dermot P.B.
AU - Schumm, L. Philip
AU - Traherne, James A.
AU - Carrington, Mary N.
AU - Kosmoliaptsis, Vasilis
AU - Karlsen, Tom H.
AU - Franke, Andre
AU - Rioux, John D.
AU - Abraham, Clara
AU - Achkar, Jean Paul
AU - Ahmad, Tariq
AU - Amininejad, Leila
AU - Ananthakrishnan, Ashwin N.
AU - Andersen, Vibeke
AU - Anderson, Carl A.
AU - Andrews, Jane M.
AU - Aumais, Guy
AU - Baidoo, Leonard
AU - Baldassano, Robert N.
AU - Balschun, Tobias
AU - Bampton, Peter A.
AU - Barclay, Murray
AU - Bayless, Theodore M.
AU - Bethge, Johannes
AU - Bis, Joshua C.
AU - Bitton, Alain
AU - Brand, Stephan
AU - Brant, Steven R.
AU - Buning, Carsten
AU - Chew, Angela
AU - Cho, Judy H.
AU - Cleynen, Isabelle
AU - Winkelmann, Juliane
N1 - Publisher Copyright:
© 2015 Nature America, Inc. All rights reserved.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including the antigen-presenting classical human leukocyte antigen (HLA) molecules. Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but they have lacked the statistical power to define the architecture of association and causal alleles. To address this, we performed high-density SNP typing of the MHC in >32,000 individuals with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1∗01:03 in both Crohn's disease and ulcerative colitis. Noteworthy differences were observed between these diseases, including a predominant role for class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response in the colonic environment in the pathogenesis of IBD.
AB - Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including the antigen-presenting classical human leukocyte antigen (HLA) molecules. Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but they have lacked the statistical power to define the architecture of association and causal alleles. To address this, we performed high-density SNP typing of the MHC in >32,000 individuals with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1∗01:03 in both Crohn's disease and ulcerative colitis. Noteworthy differences were observed between these diseases, including a predominant role for class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response in the colonic environment in the pathogenesis of IBD.
UR - http://www.scopus.com/inward/record.url?scp=84928612813&partnerID=8YFLogxK
U2 - 10.1038/ng.3176
DO - 10.1038/ng.3176
M3 - Article
C2 - 25559196
AN - SCOPUS:84928612813
SN - 1061-4036
VL - 47
SP - 172
EP - 179
JO - Nature Genetics
JF - Nature Genetics
IS - 2
ER -