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 | Zendy

Philippe Goyette | Zendy; Gabrielle Boucher | Zendy; Dermot Mallon | Zendy; Eva Ellinghaus | Zendy; Luke Jostins | Zendy; Hailiang Huang | Zendy; Stephan Ripke | Zendy; Elena S. Gusareva | Zendy; Vito Annese | Zendy; Stephen L. Hauser | Zendy; Jorge R. Oksenberg | Zendy; Ingo Thomsen | Zendy; Stephen Leslie | Zendy; Mark J. Daly | Zendy; Kristel Van Steen | Zendy; Richard H. Duerr | Zendy; Jeffrey C. Barrett | Zendy; Dermot McGovern | Zendy; L. Philip Schumm | Zendy; James A. Traherne | Zendy; Mary Carrington | Zendy; Vasilis Kosmoliaptsis | Zendy; Tom H. Karlsen | Zendy; André Franke | Zendy; John D. Rioux | Zendy

Open Access

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

Author(s) -

Philippe Goyette,

Gabrielle Boucher,

Dermot Mallon,

Eva Ellinghaus,

Luke Jostins,

Hailiang Huang,

Stephan Ripke,

Elena S. Gusareva,

Vito Annese,

Stephen L. Hauser,

Jorge R. Oksenberg,

Ingo Thomsen,

Stephen Leslie,

Mark J. Daly,

Kristel Van Steen,

Richard H. Duerr,

Jeffrey C. Barrett,

Dermot McGovern,

L. Philip Schumm,

James A. Traherne,

Mary Carrington,

Vasilis Kosmoliaptsis,

Tom H. Karlsen,

André Franke,

John D. Rioux

Publication year - 2015

Publication title -

nature genetics

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 18.861

H-Index - 573

eISSN - 1546-1718

pISSN - 1061-4036

DOI - 10.1038/ng.3176

Subject(s) - ulcerative colitis , inflammatory bowel disease , human leukocyte antigen , immunology , major histocompatibility complex , biology , allele , pathogenesis , genome wide association study , disease , snp , crohn's disease , colitis , immune system , antigen , genetics , single nucleotide polymorphism , medicine , gene , genotype

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.

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