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High-density mapping of the MHC identifies a shared role for HLA-DRB1(star)01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis

HAWKEY, CHRIS; Abraham, Clara; Goyette, Philippe; Achkar, Jean-Paul; Boucher, Gabrielle; Ahmad, Tariq; Mallon, Dermot; Amininejad, Leila; Ellinghaus, Eva; Ananthakrishnan, Ashwin N; Jostins, Luke; Andersen, Vibeke; Huang, Hailiang; Anderson, Carl A; Ripke, Stephan; Andrews, Jane M; Gusareva, Elena S; Annese, Vito; Annese, Vito; Aumais, Guy; Hauser, Stephen L; Baidoo, Leonard; Oksenberg, Jorge R; Baldassano, Robert N; Thomsen, Ingo; Balschun, Tobias; Leslie, Stephen; Bampton, Peter A; Daly, Mark J; Barclay, Murray; Van Steen, Kristel; Barrett, Jeffrey C; Duerr, Richard H; Bayless, Theodore M; Barrett, Jeffrey C; Bethge, Johannes; McGovern, Dermot P B; Bis, Joshua C; Philip Schumm, L; Bitton, Alain; Traherne, James A; Boucher, Gabrielle; Carrington, Mary N; Brand, Stephan; Kosmoliaptsis, Vasilis; Brant, Steven R; Karlsen, Tom H; B?ning, Carsten; Franke, Andre; Chew, Angela; Rioux, John D; Cho, Judy H; Cleynen, Isabelle; Cohain, Ariella; Croft, Anthony; Daly, Mark J; D?Amato, Mauro; Danes...

Authors

CHRIS HAWKEY

Clara Abraham

Philippe Goyette

Jean-Paul Achkar

Gabrielle Boucher

Tariq Ahmad

Dermot Mallon

Leila Amininejad

Eva Ellinghaus

Ashwin N Ananthakrishnan

Luke Jostins

Vibeke Andersen

Hailiang Huang

Carl A Anderson

Stephan Ripke

Jane M Andrews

Elena S Gusareva

Vito Annese

Vito Annese

Guy Aumais

Stephen L Hauser

Leonard Baidoo

Jorge R Oksenberg

Robert N Baldassano

Ingo Thomsen

Tobias Balschun

Stephen Leslie

Peter A Bampton

Mark J Daly

Murray Barclay

Kristel Van Steen

Jeffrey C Barrett

Richard H Duerr

Theodore M Bayless

Jeffrey C Barrett

Johannes Bethge

Dermot P B McGovern

Joshua C Bis

L Philip Schumm

Alain Bitton

James A Traherne

Gabrielle Boucher

Mary N Carrington

Stephan Brand

Vasilis Kosmoliaptsis

Steven R Brant

Tom H Karlsen

Carsten B�ning

Andre Franke

Angela Chew

John D Rioux

Judy H Cho

Isabelle Cleynen

Ariella Cohain

Anthony Croft

Mark J Daly

Mauro D?Amato

Silvio Danese

Dirk De Jong

Martine De Vos

Goda Denapiene

Lee A Denson

Kathy L Devaney

Olivier Dewit

Renata D?Inca

Marla Dubinsky

Richard H Duerr

Cathryn Edwards

David Ellinghaus

Jonah Essers

Lynnette R Ferguson

Eleonora A Festen

Philip Fleshner

Tim Florin

Denis Franchimont

Andre Franke

Karin Fransen

Richard Gearry

Michel Georges

Christian Gieger

J�rgen Glas

Philippe Goyette

Todd Green

Anne M Griffiths

Stephen L Guthery

Hakon Hakonarson

Jonas Halfvarson

Katherine Hanigan

Talin Haritunians

Ailsa Hart

Nicholas K Hayward

Matija Hedl

Paul Henderson

Xinli Hu

Hailiang Huang

Ken Y Hui

Marcin Imielinski

Andrew Ippoliti

Laimas Jonaitis

Luke Jostins

Tom H Karlsen

Nicholas A Kennedy

Mohammed Azam Khan

Gediminas Kiudelis

Subra Kugathasan

Limas Kupcinskas

Anna Latiano

Debby Laukens

Ian C Lawrance

James C Lee

Charlie W Lees

Marcis Leja

Johan Van Limbergen

Paolo Lionetti

Jimmy Z Liu

Edouard Louis

Gillian Mahy

John Mansfield

Dunecan Massey

Christopher G Mathew

Dermot P B McGovern

Raquel Milgrom

Mitja Mitrovic

Grant W Montgomery

Craig Mowat

William Newman

Aylwin Ng

Siew C Ng

Sok Meng Evelyn Ng

Susanna Nikolaus

Kaida Ning

Markus N�then

Ioannis Oikonomou

Orazio Palmieri

Miles Parkes

Anne Phillips

Cyriel Y Ponsioen

Ur�s Potocnik

Natalie J Prescott

Deborah D Proctor

Graham Radford-Smith

Jean-Francois Rahier

Soumya Raychaudhuri

Miguel Regueiro

Florian Rieder

John D Rioux

Stephan Ripke

Rebecca Roberts

Richard K Russell

Jeremy D Sanderson

Miquel Sans

Jack Satsangi

Eric E Schadt

Stefan Schreiber

L Philip Schumm

Regan Scott

Mark Seielstad

Yashoda Sharma

Mark S Silverberg

Lisa A Simms

Jurgita Skieceviciene

Sarah L Spain

A Hillary Steinhart

Joanne M Stempak

Laura Stronati

Jurgita Sventoraityte

Stephan R Targan

Kirstin M Taylor

Anje ter Velde

Emilie Theatre

Leif Torkvist

Mark Tremelling

Andrea van der Meulen

Suzanne van Sommeren

Eric Vasiliauskas

Severine Vermeire

Hein W Verspaget

Thomas Walters

Kai Wang

Ming-Hsi Wang

Rinse K Weersma

Zhi Wei

David Whiteman

Cisca Wijmenga

David C Wilson

Juliane Winkelmann

Ramnik J Xavier

Sebastian Zeissig

Bin Zhang

Clarence K Zhang

Hu Zhang

Wei Zhang

Hongyu Zhao

Zhen Z Zhao



Abstract

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) molecules1. 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 alleles2,3. 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.

Citation

HAWKEY, C., Abraham, C., Goyette, P., Achkar, J., Boucher, G., Ahmad, T., …Zhao, Z. Z. (2015). High-density mapping of the MHC identifies a shared role for HLA-DRB1(star)01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis. Nature Genetics, 47(2), 172–179. https://doi.org/10.1038/ng.3176

Journal Article Type Article
Acceptance Date Dec 4, 2014
Online Publication Date Jan 5, 2015
Publication Date Feb 1, 2015
Deposit Date Nov 24, 2016
Journal Nature Genetics
Print ISSN 1061-4036
Electronic ISSN 1546-1718
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 47
Issue 2
Pages 172–179
DOI https://doi.org/10.1038/ng.3176
Public URL https://nottingham-repository.worktribe.com/output/1118223
Publisher URL https://www.nature.com/articles/ng.3176
PMID 00034869

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