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.
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.
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MHC的高密度映射确定了HLA-DRB1*01：03在炎症性肠病中的共同作用和溃疡性结肠炎中的杂合优势。
DOI：
10.1038/ng.3176
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发表时间：
2015-02
期刊：
影响因子：
30.8
通讯作者：
Rioux, John D.
中科院分区：
文献类型：
--
作者：
Goyette, Philippe;Boucher, Gabrielle;Mallon, Dermot;Ellinghaust, Eva;Jostins, Luke;Huang, Hailiang;Ripke, Stephan;Gusareva, Elena S.;Annese, Vito;Hauser, Stephen L.;Oksenberg, Jorge R.;Thomsent, Ingo;Leslie, Stephen;Daly, Mark J.;Van Steen, Kristel;Duerr, Richard H.;Barrett, Jeffrey C.;McGovern, Dermot P. B.;Schumm, L. Philip;Traherne, James A.;Carrington, Mary N.;Kosmoliaptsis, Vasilis;Karsen, Tom H.;Franke, Andre;Rioux, John D.
相关的慢性炎症性肠病（IBD），称为克罗恩病和溃疡性结肠炎的全基因组关联研究显示了与主要组织相容性复合体（MHC）相关的强有力证据。该区域编码大量免疫学候选物，包括抗原呈递经典HLA分子。IBD的研究表明，在HLA和非HLA基因上存在多个独立的关联，但缺乏统计学能力来定义关联和致病等位基因的结构。为了解决这个问题，我们在> 32，000名IBD患者中进行了MHC的高密度SNP分型，涉及多个HLA等位基因，其中HLA-DRB 1 *01：03在克罗恩病和溃疡性结肠炎中起主要作用。在这些疾病之间观察到显著差异，包括在溃疡性结肠炎中观察到的II类HLA变体的主导作用和杂合优势，表明对结肠环境的适应性免疫应答在IBD的发病机制中的重要作用。
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 HLA molecules. Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but 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 patients with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1*01:03 in both Crohn’s disease and ulcerative colitis. Significant differences were observed between these diseases, including a predominant role of class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response to the colonic environment in the pathogenesis of IBD.
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影响因子：
9.8
作者：
Newman, B;Silverberg, MS;Siminovitch, K
通讯作者：
Siminovitch, K
影响因子：
4.3
作者：
Dilthey, Alexander;Leslie, Stephen;McVean, Gil
通讯作者：
McVean, Gil
影响因子：
30.8
作者：
Liu, Jimmy Z.;Hov, Johannes Roksund;Folseraas, Trine;Ellinghaus, Eva;Rushbrook, Simon M.;Doncheva, Nadezhda T.;Andreassen, Ole A.;Weersma, Rinse K.;Weismueller, Tobias J.;Eksteen, Bertus;Invernizzi, Pietro;Hirschfield, Gideon M.;Gotthardt, Daniel Nils;Pares, Albert;Ellinghaus, David;Shah, Tejas;Juran, Brian D.;Milkiewicz, Piotr;Rust, Christian;Schramm, Christoph;Mueller, Tobias;Srivastava, Brijesh;Dalekos, Georgios;Noethen, Markus M.;Herms, Stefan;Winkelmann, Juliane;Mitrovic, Mitja;Braun, Felix;Ponsioen, Cyriel Y.;Croucher, Peter J. P.;Sterneck, Martina;Teufel, Andreas;Mason, Andrew L.;Saarela, Janna;Leppa, Virpi;Dorfman, Ruslan;Alvaro, Domenico;Floreani, Annarosa;Onengut-Gumuscu, Suna;Rich, Stephen S.;Thompson, Wesley K.;Schork, Andrew J.;Naess, Sigrid;Thomsen, Ingo;Mayr, Gabriele;Koenig, Inke R.;Hveem, Kristian;Cleynen, Isabelle;Gutierrez-Achury, Javier;Ricano-Ponce, Isis;van Heel, David;Bjoernsson, Einar;Sandford, Richard N.;Durie, Peter R.;Melum, Espen;Vatn, Morten H.;Silverberg, Mark S.;Duerr, Richard H.;Padyukov, Leonid;Brand, Stephan;Sans, Miquel;Annese, Vito;Achkar, Jean-Paul;Boberg, Kirsten Muri;Marschall, Hanns-Ulrich;Chazouilleres, Olivier;Bowlus, Christopher L.;Wijmenga, Cisca;Schrumpf, Erik;Vermeire, Severine;Albrecht, Mario;Rioux, John D.;Alexander, Graeme;Bergquist, Annika;Cho, Judy;Schreiber, Stefan;Manns, Michael P.;Farkkila, Martti;Dale, Anders M.;Chapman, Roger W.;Lazaridis, Konstantinos N.;Franke, Andre;Anderson, Carl A.;Karlsen, Tom H.
通讯作者：
Karlsen, Tom H.
影响因子：
15.9
作者：
ALPER, CA;FLEISCHNICK, E;YUNIS, EJ
通讯作者：
YUNIS, EJ
DOI：
10.1073/pnas.0909307106
发表时间：
2009-11-03
影响因子：
11.1
作者：
Rioux, John D.;Goyette, Philippe;Hauser, Stephen L.
通讯作者：
Hauser, Stephen L.