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

Jostins, Luke, Ripke, Stephan, Weersma, Rinse K., Duerr, Richard H., McGovern, Dermot P., Hui, Ken Y., Lee, James C., Schumm, L. Philip, Sharma, Yashoda, Anderson, Carl A., Essers, Jonah, Mitrovic, Mitja, Ning, Kaida, Cleynen, Isabelle, Theatre, Emilie, Spain, Sarah L., Raychaudhuri, Soumya, Goyette, Philippe, Wei, Zhi, Abraham, Clara, Achkar, Jean-Paul, Ahmad, Tariq, Amininejad, Leila, Ananthakrishnan, Ashwin N., Andersen, Vibeke, Andrews, Jane M., Baidoo, Leonard, Balschun, Tobias, Bampton, Peter A., Bitton, Alain, Boucher, Gabrielle, Brand, Stephan, Buening, Carsten, Cohain, Ariella, Cichon, Sven, D'Amato, Mauro, De Jong, Dirk, Devaney, Kathy L., Dubinsky, Marla, Edwards, Cathryn, Ellinghaus, David, Ferguson, Lynnette R., Franchimont, Denis, Fransen, Karin, Gearry, Richard, Georges, Michel, Gieger, Christian, Glas, Juergen, Haritunians, Talin, Hart, Ailsa, Hawkey, Chris, Hedl, Matija, Hu, Xinli, Karlsen, Tom H., Kupcinskas, Limas, Kugathasan, Subra, Latiano, Anna, Laukens, Debby, Lawrance, Ian C., Lees, Charlie W., Louis, Edouard, Mahy, Gillian, Mansfield, John, Morgan, Angharad R., Mowat, Craig, Newman, William, Palmieri, Orazio, Ponsioen, Cyriel Y., Potocnik, Uros, Prescott, Natalie J., Regueiro, Miguel, Rotter, Jerome I., Russell, Richard K., Sanderson, Jeremy D., Sans, Miquel, Satsangi, Jack, Schreiber, Stefan, Simms, Lisa A., Sventoraityte, Jurgita, Targan, Stephan R., Taylor, Kent D., Tremelling, Mark, Verspaget, Hein W., De Vos, Martine, Wijmenga, Cisca, Wilson, David C., Winkelmann, Juliane, Xavier, Ramnik J., Zeissig, Sebastian, Zhang, Bin, Zhang, Clarence K., Zhao, Hongyu, Silverberg, Mark S., Annese, Vito, Hakonarson, Hakon, Brant, Steven R., Radford-Smith, Graham, Mathew, Christopher G., Rioux, John D., Schadt, Eric E., Daly, Mark J., Franke, Andre, Parkes, Miles, Vermeire, Severine, Barrett, Jeffrey C. and Cho, Judy H. (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature, 491 7422: 119-124. doi:10.1038/nature11582

Author Jostins, Luke
Ripke, Stephan
Weersma, Rinse K.
Duerr, Richard H.
McGovern, Dermot P.
Hui, Ken Y.
Lee, James C.
Schumm, L. Philip
Sharma, Yashoda
Anderson, Carl A.
Essers, Jonah
Mitrovic, Mitja
Ning, Kaida
Cleynen, Isabelle
Theatre, Emilie
Spain, Sarah L.
Raychaudhuri, Soumya
Goyette, Philippe
Wei, Zhi
Abraham, Clara
Achkar, Jean-Paul
Ahmad, Tariq
Amininejad, Leila
Ananthakrishnan, Ashwin N.
Andersen, Vibeke
Andrews, Jane M.
Baidoo, Leonard
Balschun, Tobias
Bampton, Peter A.
Bitton, Alain
Boucher, Gabrielle
Brand, Stephan
Buening, Carsten
Cohain, Ariella
Cichon, Sven
D'Amato, Mauro
De Jong, Dirk
Devaney, Kathy L.
Dubinsky, Marla
Edwards, Cathryn
Ellinghaus, David
Ferguson, Lynnette R.
Franchimont, Denis
Fransen, Karin
Gearry, Richard
Georges, Michel
Gieger, Christian
Glas, Juergen
Haritunians, Talin
Hart, Ailsa
Hawkey, Chris
Hedl, Matija
Hu, Xinli
Karlsen, Tom H.
Kupcinskas, Limas
Kugathasan, Subra
Latiano, Anna
Laukens, Debby
Lawrance, Ian C.
Lees, Charlie W.
Louis, Edouard
Mahy, Gillian
Mansfield, John
Morgan, Angharad R.
Mowat, Craig
Newman, William
Palmieri, Orazio
Ponsioen, Cyriel Y.
Potocnik, Uros
Prescott, Natalie J.
Regueiro, Miguel
Rotter, Jerome I.
Russell, Richard K.
Sanderson, Jeremy D.
Sans, Miquel
Satsangi, Jack
Schreiber, Stefan
Simms, Lisa A.
Sventoraityte, Jurgita
Targan, Stephan R.
Taylor, Kent D.
Tremelling, Mark
Verspaget, Hein W.
De Vos, Martine
Wijmenga, Cisca
Wilson, David C.
Winkelmann, Juliane
Xavier, Ramnik J.
Zeissig, Sebastian
Zhang, Bin
Zhang, Clarence K.
Zhao, Hongyu
Silverberg, Mark S.
Annese, Vito
Hakonarson, Hakon
Brant, Steven R.
Radford-Smith, Graham
Mathew, Christopher G.
Rioux, John D.
Schadt, Eric E.
Daly, Mark J.
Franke, Andre
Parkes, Miles
Vermeire, Severine
Barrett, Jeffrey C.
Cho, Judy H.
Title Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
Publication date 2012-11-01
Year available 2012
Sub-type Article (original research)
DOI 10.1038/nature11582
Open Access Status Not yet assessed
Volume 491
Issue 7422
Start page 119
End page 124
Total pages 6
Place of publication London, United Kingdom
Publisher Nature
Language eng
Subject 1000 General
Abstract 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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