Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease

Luke Jostins; Stephan Ripke; Rinse K. Weersma; Richard H. Duerr; Dermot P. McGovern; Ken Y. Hui; James C. Lee; L. Philip Schumm; Yashoda Sharma; Carl A. Anderson; Jonah Essers; Mitja Mitrovic; Kaida Ning; Isabelle Cleynen; Emilie Theatre; Sarah L. Spain; Soumya Raychaudhuri; Philippe Goyette; Zhi Wei; Clara Abraham; Jean-Paul Achkar; Tariq Ahmad; Leila Amininejad; Ashwin N. Ananthakrishnan; Vibeke Andersen; Jane M. Andrews; Leonard Baidoo; Tobias Balschun; Peter A. Bampton; Alain Bitton; Gabrielle Boucher; Stephan Brand; Carsten Buening; Ariella Cohain; Sven Cichon; Mauro D'Amato; Dirk De Jong; Kathy L. Devaney; Marla Dubinsky; Cathryn Edwards; David Ellinghaus; Lynnette R. Ferguson; Denis Franchimont; Karin Fransen; Richard Gearry; Michel Georges; Christian Gieger; Juergen Glas; Talin Haritunians; Ailsa Hart; Chris Hawkey; Matija Hedl; Xinli Hu; Tom H. Karlsen; Limas Kupcinskas; Subra Kugathasan; Anna Latiano; Debby Laukens; Ian C. Lawrance; Charlie W. Lees; Edouard Louis; Gillian Mahy; John Mansfield; Angharad R. Morgan; Craig Mowat; William Newman; Orazio Palmieri; Cyriel Y. Ponsioen; Uros Potocnik; Natalie J. Prescott; Miguel Regueiro; Jerome I. Rotter; Richard K. Russell; Jeremy D. Sanderson; Miquel Sans; Jack Satsangi; Stefan Schreiber; Lisa A. Simms; Jurgita Sventoraityte; Stephan R. Targan; Kent D. Taylor; Mark Tremelling; Hein W. Verspaget; Martine De Vos; Cisca Wijmenga; David C. Wilson; Juliane Winkelmann; Ramnik J. Xavier; Sebastian Zeissig; Bin Zhang; Clarence K. Zhang; Hongyu Zhao; Mark S. Silverberg; Vito Annese; Hakon Hakonarson; Steven R. Brant; Graham Radford-Smith; Christopher G. Mathew; John D. Rioux; Eric E. Schadt; Int IBD Genetics Consortium IIBDGC; Inga Prokopenko

doi:10.1038/nature11582

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Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease

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Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease

Luke Jostins, Stephan Ripke, Rinse K. Weersma, Richard H. Duerr, Dermot P. McGovern, Ken Y. Hui, James C. Lee, L. Philip Schumm, Yashoda Sharma, Carl A. Anderson, …

Nature (London), Vol.491(7422), pp.119-124

01/11/2012

DOI: https://doi.org/10.1038/nature11582

PMID: 23128233

Abstract

Multidisciplinary Sciences

Science & Technology

Science & Technology - Other Topics

Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations(1). Genome-wide association studies and subsequent meta-analyses of these two diseases(2,3) as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy(4), in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases(5). Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

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Title: Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease
Creators: Luke Jostins - Wellcome Sanger Institute
Stephan Ripke - Massachusetts General Hospital
Rinse K. Weersma - University Medical Center Groningen
Richard H. Duerr - University of Pittsburgh
Dermot P. McGovern - F Widjaja Fdn Inflammatory Bowel, Los Angeles, CA 90048 USA
Ken Y. Hui - Yale University
James C. Lee - Addenbrooke's Hospital
L. Philip Schumm - University of Chicago
Yashoda Sharma - Yale University
Carl A. Anderson - Wellcome Sanger Institute
Jonah Essers - Center for Human Genetics
Mitja Mitrovic - University of Maribor
Kaida Ning - Yale University
Isabelle Cleynen - KU Leuven
Emilie Theatre - University of Liège
Sarah L. Spain - King's College London
Soumya Raychaudhuri - Brigham and Women's Hospital
Philippe Goyette - Montreal Heart Institute
Zhi Wei - New Jersey Institute of Technology
Clara Abraham - Yale University
Jean-Paul Achkar - Cleveland Clin, Dept Gastroenterol & Hepatol, Inst Digest Dis, Cleveland, OH 44195 USA
Tariq Ahmad - Peninsula College of Medicine and Dentistry
Leila Amininejad - Erasmus Hospital
Ashwin N. Ananthakrishnan - Massachusetts General Hospital
Vibeke Andersen - Regionshospitalet Viborg
Jane M. Andrews - Royal Adelaide Hospital
Leonard Baidoo - University of Pittsburgh
Tobias Balschun - Kiel University
Peter A. Bampton - Flinders Medical Centre
Alain Bitton - McGill University Health Centre
Gabrielle Boucher - Montreal Heart Institute
Stephan Brand - Ludwig-Maximilians-Universität München
Carsten Buening - Charité - Universitätsmedizin Berlin
Ariella Cohain - Icahn School of Medicine at Mount Sinai
Sven Cichon - Life & Brain
Mauro D'Amato - Karolinska Institutet
Dirk De Jong - University Medical Center Groningen
Kathy L. Devaney - Massachusetts General Hospital
Marla Dubinsky - Cedars-Sinai Medical Center
Cathryn Edwards - Torbay Hospital
David Ellinghaus - Kiel University
Lynnette R. Ferguson - University of Auckland
Denis Franchimont - Erasmus Hospital
Karin Fransen - University of Pittsburgh
Richard Gearry - University of Otago
Michel Georges - University of Liège
Christian Gieger - Helmholtz Zentrum München
Juergen Glas - McGill University
Talin Haritunians - Cedars-Sinai Medical Center
Ailsa Hart - St Mark's Hospital
Chris Hawkey - NIHR Nottingham Digestive Diseases Biomedical Research Unit
Matija Hedl - Yale University
Xinli Hu - Brigham and Women's Hospital
Tom H. Karlsen - Oslo University Hospital
Limas Kupcinskas - College Station Medical Center
Subra Kugathasan - Emory University
Anna Latiano - Casa Sollievo della Sofferenza
Debby Laukens - Ghent University Hospital
Ian C. Lawrance - University of Western Australia
Charlie W. Lees - Western General Hospital
Edouard Louis - Centre Hospitalier Universitaire de Liège
Gillian Mahy - Townsville Hospital
John Mansfield - Newcastle University
Angharad R. Morgan - University of Auckland
Craig Mowat - Ninewells Hospital
William Newman - University of Manchester
Orazio Palmieri - Casa Sollievo della Sofferenza
Cyriel Y. Ponsioen - Academic Medical Center
Uros Potocnik - University of Maribor
Natalie J. Prescott - Guy's Hospital
Miguel Regueiro - University of Pittsburgh
Jerome I. Rotter - Cedars-Sinai Medical Center
Richard K. Russell - Royal Hospital for Children
Jeremy D. Sanderson - St Thomas' Hospital
Miquel Sans - Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
Jack Satsangi - University of Edinburgh
Stefan Schreiber - Kiel University
Lisa A. Simms - QIMR Berghofer Medical Research Institute
Jurgita Sventoraityte - College Station Medical Center
Stephan R. Targan - F Widjaja Fdn Inflammatory Bowel, Los Angeles, CA 90048 USA
Kent D. Taylor - Cedars-Sinai Medical Center
Mark Tremelling - Norfolk and Norwich University Hospital
Hein W. Verspaget - Leiden University Medical Center
Martine De Vos - Ghent University
Cisca Wijmenga - University of Groningen
David C. Wilson - Royal Hospital for Children
Juliane Winkelmann - Technical University of Munich
Ramnik J. Xavier - Massachusetts General Hospital
Sebastian Zeissig - College Station Medical Center
Bin Zhang - Icahn School of Medicine at Mount Sinai
Clarence K. Zhang - Yale University
Hongyu Zhao - Yale University
Mark S. Silverberg - Mount Sinai Hospital
Vito Annese - Casa Sollievo della Sofferenza
Hakon Hakonarson - Children's Hospital of Philadelphia
Steven R. Brant - Johns Hopkins University
Graham Radford-Smith - College Station Medical Center
Christopher G. Mathew - King's College London
John D. Rioux - Montreal Heart Institute
Eric E. Schadt - Icahn School of Medicine at Mount Sinai
Int IBD Genetics Consortium IIBDGC
Inga Prokopenko - School of Biosciences
Publication Details: Nature (London), Vol.491(7422), pp.119-124
Publisher: Springer Nature
Number of pages: 6
Date published: 01/11/2012
Grant note: Else Kroner-Fresenius-Stiftung (Else Kroner-Exzellenzstipendium) Italian Society for Paediatric Gastroenterology, Hepatology and Nutrition German Federal Ministry of Education and Research (BMBF); Federal Ministry of Education & Research (BMBF) FR 2821/2-1; BR 1912/6-1 / DFG; German Research Foundation (DFG) G0000934 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) BSIK03009 / Celiac Disease Consortium Swedish National Program for IBD Genetics M11-1 / Crohn's and Colitis UK; Crohn's & Colitis Foundation of America National Institute for Health Research, through the Comprehensive Local Research Network Crohn's and Colitis Foundation of America; Crohn's & Colitis Foundation of America
Identifiers: 99928814802346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease

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