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

Author

Listed:
  • Luke Jostins

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.)

  • Stephan Ripke

    (Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Rinse K. Weersma

    (University of Groningen and University Medical Center Groningen, Groningen 9700 RB, The Netherlands.)

  • Richard H. Duerr

    (Hepatology and Nutrition, University of Pittsburgh School of Medicine
    University of Pittsburgh Graduate School of Public Health)

  • Dermot P. McGovern

    (F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute
    Medical Genetics Institute, Cedars-Sinai Medical Center)

  • Ken Y. Hui

    (Yale School of Medicine, New Haven, Connecticut 06520, USA.)

  • James C. Lee

    (Inflammatory Bowel Disease Research Group, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, UK.)

  • L. Philip Schumm

    (University of Chicago)

  • Yashoda Sharma

    (Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut 06520, USA.)

  • Carl A. Anderson

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.)

  • Jonah Essers

    (Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School)

  • Mitja Mitrovic

    (University of Maribor, Faculty of Medicine, Center for Human Molecular Genetics and Pharmacogenomics, Maribor 2000, Slovenia.
    University Medical Center Groningen, Groningen 9700 RB, The Netherlands.)

  • Kaida Ning

    (Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut 06520, USA.)

  • Isabelle Cleynen

    (Gastroenterology section, KU Leuven, Leuven 3000, Belgium.)

  • Emilie Theatre

    (Unit of Animal Genomics, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA-R) and Faculty of Veterinary Medicine, University of Liège, Liège 4000, Belgium.
    Centre Hospitalier Universitaire, Université de Liège, Liège 4000, Belgium.)

  • Sarah L. Spain

    (King’s College London School of Medicine, Guy’s Hospital, London SE1 9RT, UK.)

  • Soumya Raychaudhuri

    (Brigham and Women’s Hospital
    Program in Medical and Population Genetics, Broad Institute
    Brigham and Women’s Hospital)

  • Philippe Goyette

    (Université de Montréal and the Montreal Heart Institute, Research Center, Montréal, Québec H1T 1C8, Canada.)

  • Zhi Wei

    (New Jersey Institute of Technology, Newark, New Jersey 07102, USA.)

  • Clara Abraham

    (Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut 06520, USA.)

  • Jean-Paul Achkar

    (Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
    Lerner Research Institute, Cleveland Clinic)

  • Tariq Ahmad

    (Peninsula College of Medicine and Dentistry, Exeter EX1 2LU, UK.)

  • Leila Amininejad

    (Erasmus Hospital, Free University of Brussels, Brussels, 1070 Belgium.)

  • Ashwin N. Ananthakrishnan

    (Massachusetts General Hospital, Harvard Medical School, Gastroenterology Unit)

  • Vibeke Andersen

    (Viborg Regional Hospital, Viborg 8800, Denmark.)

  • Jane M. Andrews

    (Inflammatory Bowel Disease Service, Royal Adelaide Hospital, and School of Medicine, University of Adelaide, Adelaide 5000, Australia.)

  • Leonard Baidoo

    (Hepatology and Nutrition, University of Pittsburgh School of Medicine)

  • Tobias Balschun

    (Institute of Clinical Chemistry, Christian-Albrechts-University, Kiel 24105, Germany.)

  • Peter A. Bampton

    (Flinders Medical Centre and School of Medicine, Flinders University, Adelaide 5000, Australia.)

  • Alain Bitton

    (McGill University Health Centre, Royal Victoria Hospital, Montréal, Québec H3A 1A1, Canada.)

  • Gabrielle Boucher

    (Université de Montréal and the Montreal Heart Institute, Research Center, Montréal, Québec H1T 1C8, Canada.)

  • Stephan Brand

    (University Hospital Munich-Grosshadern, Ludwig-Maximilians-University, Munich 80336, Germany.)

  • Carsten Büning

    (Charité, Campus Mitte, Universitätsmedizin Berlin, Berlin 10117, Germany.)

  • Ariella Cohain

    (Mount Sinai School of Medicine)

  • Sven Cichon

    (Life & Brain Center, University Hospital Bonn, Bonn 53012, Germany.)

  • Mauro D’Amato

    (Karolinska Institutet, Stockholm 14 183, Sweden.)

  • Dirk De Jong

    (University of Groningen and University Medical Center Groningen, Groningen 9700 RB, The Netherlands.)

  • Kathy L. Devaney

    (Massachusetts General Hospital, Harvard Medical School, Gastroenterology Unit)

  • Marla Dubinsky

    (Cedars Sinai Medical Center)

  • Cathryn Edwards

    (Torbay Hospital, Torbay, Devon TQ2 7AA, UK.)

  • David Ellinghaus

    (Institute of Clinical Chemistry, Christian-Albrechts-University, Kiel 24105, Germany.)

  • Lynnette R. Ferguson

    (School of Medical Sciences, Faculty of Medical & Health Sciences, The University of Auckland, Auckland 1142, New Zealand.)

  • Denis Franchimont

    (Erasmus Hospital, Free University of Brussels, Brussels, 1070 Belgium.)

  • Karin Fransen

    (Hepatology and Nutrition, University of Pittsburgh School of Medicine
    University of Groningen, University Medical Center Groningen, Groningen T9700 RB, The Netherlands.)

  • Richard Gearry

    (University of Otago, Christchurch 8140, New Zealand.
    Christchurch Hospital, Christchurch 8011, New Zealand.)

  • Michel Georges

    (Unit of Animal Genomics, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA-R) and Faculty of Veterinary Medicine, University of Liège, Liège 4000, Belgium.)

  • Christian Gieger

    (Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg 85764, Germany.)

  • Jürgen Glas

    (McGill University Health Centre, Royal Victoria Hospital, Montréal, Québec H3A 1A1, Canada.)

  • Talin Haritunians

    (Medical Genetics Institute, Cedars-Sinai Medical Center)

  • Ailsa Hart

    (St Mark’s Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK.)

  • Chris Hawkey

    (Nottingham Digestive Diseases Centre, Queens Medical Centre, Nottingham NG7 1AW, UK.)

  • Matija Hedl

    (Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut 06520, USA.)

  • Xinli Hu

    (Brigham and Women’s Hospital)

  • Tom H. Karlsen

    (Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo 0424, Norway.)

  • Limas Kupcinskas

    (Kaunas University of Medicine, Kaunas 44307, Lithuania.)

  • Subra Kugathasan

    (Emory University School of Medicine)

  • Anna Latiano

    (Unit of Gastroenterology, Istituto di Ricovero e Cura a Carattere Scientifico-Casa Sollievo della Sofferenza (IRCCS-CSS) Hospital, San Giovanni Rotondo 71013, Italy.)

  • Debby Laukens

    (Ghent University Hospital, Ghent 9000, Belgium.)

  • Ian C. Lawrance

    (School of Medicine and Pharmacology, The University of Western Australia, Fremantle, Western Australia 6009, Australia.)

  • Charlie W. Lees

    (Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.)

  • Edouard Louis

    (Centre Hospitalier Universitaire, Université de Liège, Liège 4000, Belgium.)

  • Gillian Mahy

    (The Townsville Hospital)

  • John Mansfield

    (Institute of Human Genetics, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.)

  • Angharad R. Morgan

    (School of Medical Sciences, Faculty of Medical & Health Sciences, The University of Auckland, Auckland 1142, New Zealand.)

  • Craig Mowat

    (Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.)

  • William Newman

    (Genetic Medicine, MAHSC, University of Manchester, Manchester M13 9PL, UK.)

  • Orazio Palmieri

    (Unit of Gastroenterology, Istituto di Ricovero e Cura a Carattere Scientifico-Casa Sollievo della Sofferenza (IRCCS-CSS) Hospital, San Giovanni Rotondo 71013, Italy.)

  • Cyriel Y. Ponsioen

    (Academic Medical Center, Amsterdam 1105 AZ, The Netherlands.)

  • Uros Potocnik

    (University of Maribor, Faculty of Medicine, Center for Human Molecular Genetics and Pharmacogenomics, Maribor 2000, Slovenia.
    University of Maribor, Faculty for Chemistry and Chemical Engineering, Maribor 2000, Slovenia.)

  • Natalie J. Prescott

    (King’s College London School of Medicine, Guy’s Hospital, London SE1 9RT, UK.)

  • Miguel Regueiro

    (Hepatology and Nutrition, University of Pittsburgh School of Medicine)

  • Jerome I. Rotter

    (Medical Genetics Institute, Cedars-Sinai Medical Center)

  • Richard K. Russell

    (Royal Hospital for Sick Children, Paediatric Gastroenterology and Nutrition, Glasgow G3 8SJ, UK.)

  • Jeremy D. Sanderson

    (Guy’s & St Thomas’ NHS Foundation Trust, St Thomas’ Hospital, London SE1 7EH, UK.)

  • Miquel Sans

    (Hospital Clinic/Institut d’Investigacions Biomédiques August Pi i Sunyer (IDIBAPS)
    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBER-EHD), Barcelona 08036, Spain.)

  • Jack Satsangi

    (Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.)

  • Stefan Schreiber

    (Institute of Clinical Chemistry, Christian-Albrechts-University, Kiel 24105, Germany.
    Christian-Albrechts-University, Kiel, Kiel 24118, Germany.)

  • Lisa A. Simms

    (Inflammatory Bowel Diseases, Genetics and Computational Biology, Queensland Institute of Medical Research, Brisbane 4029, Australia.)

  • Jurgita Sventoraityte

    (Kaunas University of Medicine, Kaunas 44307, Lithuania.)

  • Stephan R. Targan

    (F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute)

  • Kent D. Taylor

    (F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute
    Medical Genetics Institute, Cedars-Sinai Medical Center)

  • Mark Tremelling

    (Norfolk and Norwich University Hospital, Norwich NR4 7UY, UK.)

  • Hein W. Verspaget

    (Leiden University Medical Center, Leiden 2333 ZA, The Netherlands.)

  • Martine De Vos

    (Ghent University Hospital, Ghent 9000, Belgium.)

  • Cisca Wijmenga

    (University of Groningen, University Medical Center Groningen, Groningen T9700 RB, The Netherlands.)

  • David C. Wilson

    (Royal Hospital for Sick Children, Paediatric Gastroenterology and Nutrition, Glasgow G3 8SJ, UK.
    Child Life and Health, University of Edinburgh, Edinburgh, Scotland EH9 1UW, UK.)

  • Juliane Winkelmann

    (Technische Universität München, Munich 80336, Germany.)

  • Ramnik J. Xavier

    (Massachusetts General Hospital, Harvard Medical School, Gastroenterology Unit
    Center for Computational and Integrative Biology, Massachusetts General Hospital)

  • Sebastian Zeissig

    (Christian-Albrechts-University, Kiel, Kiel 24118, Germany.)

  • Bin Zhang

    (Mount Sinai School of Medicine)

  • Clarence K. Zhang

    (School of Public Health, Yale University, New Haven, Connecticut 06520, USA.)

  • Hongyu Zhao

    (School of Public Health, Yale University, New Haven, Connecticut 06520, USA.)

  • Mark S. Silverberg

    (Mount Sinai Hospital Inflammatory Bowel Disease Centre, University of Toronto, Toronto, Ontario M5G 1X5, Canada.)

  • Vito Annese

    (Unit of Gastroenterology, Istituto di Ricovero e Cura a Carattere Scientifico-Casa Sollievo della Sofferenza (IRCCS-CSS) Hospital, San Giovanni Rotondo 71013, Italy.
    Azienda Ospedaliero Universitaria (AOU) Careggi, Unit of Gastroenterology SOD2, Florence 50134, Italy.)

  • Hakon Hakonarson

    (Center for Applied Genomics, The Children’s Hospital of Philadelphia
    Center for Pediatric Inflammatory Bowel Disease, The Children’s Hospital of Philadelphia)

  • Steven R. Brant

    (Meyerhoff Inflammatory Bowel Disease Center, School of Medicine, Bloomberg School of Public Health, Johns Hopkins University)

  • Graham Radford-Smith

    (Inflammatory Bowel Diseases, Genetics and Computational Biology, Queensland Institute of Medical Research, Brisbane 4029, Australia.
    Royal Brisbane and Women’s Hospital, and School of Medicine, University of Queensland)

  • Christopher G. Mathew

    (King’s College London School of Medicine, Guy’s Hospital, London SE1 9RT, UK.)

  • John D. Rioux

    (Université de Montréal and the Montreal Heart Institute, Research Center, Montréal, Québec H1T 1C8, Canada.)

  • Eric E. Schadt

    (Mount Sinai School of Medicine)

  • Mark J. Daly

    (Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Andre Franke

    (Institute of Clinical Chemistry, Christian-Albrechts-University, Kiel 24105, Germany.)

  • Miles Parkes

    (Inflammatory Bowel Disease Research Group, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, UK.)

  • Severine Vermeire

    (Gastroenterology section, KU Leuven, Leuven 3000, Belgium.
    University Hospital Leuven, Leuven 3000, Belgium)

  • Jeffrey C. Barrett

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.)

  • Judy H Cho

    (Yale School of Medicine, New Haven, Connecticut 06520, USA.
    Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut 06520, USA.)

Abstract

A meta-analysis of previous genome-wide association studies of Crohn’s disease and ulcerative colitis, the two most common forms of inflammatory bowel disease, with a combined total of more than 75,000 cases and controls, finds that most loci contribute to both phenotypes and other immune-mediated disorders.

Suggested Citation

  • 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 Mitrov, 2012. "Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease," Nature, Nature, vol. 491(7422), pages 119-124, November.
    • Handle: RePEc:nat:nature:v:491:y:2012:i:7422:d:10.1038_nature11582
    DOI: 10.1038/nature11582
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    Cited by:

    1. Grigory Ryzhakov & Hannah Almuttaqi & Alastair L. Corbin & Dorothée L. Berthold & Tariq Khoyratty & Hayley L. Eames & Samuel Bullers & Claire Pearson & Zhichao Ai & Kristina Zec & Sarah Bonham & Roman, 2021. "Defactinib inhibits PYK2 phosphorylation of IRF5 and reduces intestinal inflammation," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    2. Kerstin Thriene & Karin B. Michels, 2023. "Human Gut Microbiota Plasticity throughout the Life Course," IJERPH, MDPI, vol. 20(2), pages 1-14, January.
    3. Hung-Yu Chiang & Hsueh-Han Lu & Janaki N. Sudhakar & Yu-Wen Chen & Nien-Shin Shih & Yi-Ting Weng & Jr-Wen Shui, 2022. "IL-22 initiates an IL-18-dependent epithelial response circuit to enforce intestinal host defence," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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