DOI: 10.1038/nature11582

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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 McGovern,Ken Hui,James C. Lee,L. Philip Schumm,Yashoda Sharma,Carl A. Anderson,Jonah Essers,Mitja Mitrovič,Kaida Ning,Isabelle Cleynen,Emilie Théâtre,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 Büning,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 Fransén,Richard B. Gearry,Michel Georges,Christian Gieger,Jürgen Glas,Talin Haritunians,Ailsa Hart,Chris J. Hawkey,Matija Hedl,Xinli Hu,Tom H. Karlsen,Limas Kupčinskas,Subra Kugathasan,Anna Latiano,Debby Laukens,Ian C. Lawrance,Charlie W Lees,Édouard Louis,Gillian Mahy,John C. Mansfield,Ann W Morgan,Craig Mowat,William G. Newman,Orazio Palmieri,Cyriel Y. Ponsioen,Uroš Potočnik,Natalie J. Prescott,Miguel Regueiro,Jerome I. Rotter,Richard K. Russell,Jeremy Sanderson,Miquel Sans,Jack Satsangi,Stefan Schreiber,Lisa A. Simms,Jurgita Šventoraitytė,Stephan R. Targan,Kent D. Taylor,Mark Tremelling,Hein W. Verspaget,Paul Martin,Cisca Wijmenga,David C. Wilson,Juliane Winkelmann,Ramnik J. Xavier,Sebastian Zeißig,Bin Zhang,Clarence K. Zhang,Hongyu Zhao,Mark S. Silverberg,Vito Annese,Hákon Hákonarson,Steven R. Brant,Graham Radford‐Smith,Christopher G. Mathew,John D. Rioux,Eric E. Schadt,Mark J. Daly,André Franke,Miles Parkes,Séverine Vermeire,Jeffrey C. Barrett,Judy H. Cho

Genome-wide association study

Inflammatory bowel disease

Allele

2012

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. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. 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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“Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease” is a paper by Luke Jostins Stephan Ripke Rinse K. Weersma Richard H. Duerr Dermot McGovern Ken Hui James C. Lee L. Philip Schumm Yashoda Sharma Carl A. Anderson Jonah Essers Mitja Mitrovič Kaida Ning Isabelle Cleynen Emilie Théâtre 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 Büning 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 Fransén Richard B. Gearry Michel Georges Christian Gieger Jürgen Glas Talin Haritunians Ailsa Hart Chris J. Hawkey Matija Hedl Xinli Hu Tom H. Karlsen Limas Kupčinskas Subra Kugathasan Anna Latiano Debby Laukens Ian C. Lawrance Charlie W Lees Édouard Louis Gillian Mahy John C. Mansfield Ann W Morgan Craig Mowat William G. Newman Orazio Palmieri Cyriel Y. Ponsioen Uroš Potočnik Natalie J. Prescott Miguel Regueiro Jerome I. Rotter Richard K. Russell Jeremy Sanderson Miquel Sans Jack Satsangi Stefan Schreiber Lisa A. Simms Jurgita Šventoraitytė Stephan R. Targan Kent D. Taylor Mark Tremelling Hein W. Verspaget Paul Martin Cisca Wijmenga David C. Wilson Juliane Winkelmann Ramnik J. Xavier Sebastian Zeißig Bin Zhang Clarence K. Zhang Hongyu Zhao Mark S. Silverberg Vito Annese Hákon Hákonarson Steven R. Brant Graham Radford‐Smith Christopher G. Mathew John D. Rioux Eric E. Schadt Mark J. Daly André Franke Miles Parkes Séverine Vermeire Jeffrey C. Barrett Judy H. Cho published in 2012. It has an Open Access status of “green”. You can read and download a PDF Full Text of this paper here.