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

(2012) NATURE. 491(7422). p.119-124
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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(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.
Keywords
NETWORK, NUMBER, TUBERCULOSIS, MUTATIONS, HYPER-IGE SYNDROME, SUSCEPTIBILITY, RISK LOCI, METAANALYSIS, EXPRESSION

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Chicago
Jostins, Luke, Stephan Ripke, Rinse K Weersma, Richard H Duerr, Dermot P McGovern, Ken Y Hui, James C Lee, et al. 2012. “Host-microbe Interactions Have Shaped the Genetic Architecture of Inflammatory Bowel Disease.” Nature 491 (7422): 119–124.
APA
Jostins, L., Ripke, S., Weersma, R. K., Duerr, R. H., McGovern, D. P., Hui, K. Y., Lee, J. C., et al. (2012). Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. NATURE, 491(7422), 119–124.
Vancouver
1.
Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. NATURE. 2012;491(7422):119–24.
MLA
Jostins, Luke, Stephan Ripke, Rinse K Weersma, et al. “Host-microbe Interactions Have Shaped the Genetic Architecture of Inflammatory Bowel Disease.” NATURE 491.7422 (2012): 119–124. Print.
@article{3157455,
  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(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.},
  author       = {Jostins, Luke and Ripke, Stephan and Weersma, Rinse K and Duerr, Richard H and McGovern, Dermot P and Hui, Ken Y and Lee, James C and Schumm, L Philip and Sharma, Yashoda and Anderson, Carl A and Essers, Jonah and Mitrovic, Mitja and Ning, Kaida and Cleynen, Isabelle and Theatre, Emilie and Spain, Sarah L and Raychaudhuri, Soumya and Goyette, Philippe and Wei, Zhi and Abraham, Clara and Achkar, Jean-Paul and Ahmad, Tariq and Amininejad, Leila and Ananthakrishnan, Ashwin N and Andersen, Vibeke and Andrews, Jane M and Baidoo, Leonard and Balschun, Tobias and Bampton, Peter A and Bitton, Alain and Boucher, Gabrielle and Brand, Stephan and B{\"u}ning, Carsten and Cohain, Ariella and Cichon, Sven and D'Amato, Mauro and De Jong, Dirk and Devaney, Kathy L and Dubinsky, Marla and Edwards, Cathryn and Ellinghaus, David and Ferguson, Lynnette R and Franchimont, Denis and Fransen, Karin and Gearry, Richard and Georges, Michel and Gieger, Christian and Glas, J{\"u}rgen and Haritunians, Talin and Hart, Ailsa and Hawkey, Chris and Hedl, Matija and Hu, Xinli and Karlsen, Tom H and Kupcinskas, Limas and Kugathasan, Subra and Latiano, Anna and Laukens, Debby and Lawrance, Ian C and Lees, Charlie W and Louis, Edouard and Mahy, Gillian and Mansfield, John and Morgan, Angharad R and Mowat, Craig and Newman, William and Palmieri, Orazio and Ponsioen, Cyriel Y and Potocnik, Uros and Prescott, Natalie J and Regueiro, Miguel and Rotter, Jerome I and Russell, Richard K and Sanderson, Jeremy D and Sans, Miquel and Satsangi, Jack and Schreiber, Stefan and Simms, Lisa A and Sventoraityte, Jurgita and Targan, Stephan R and Taylor, Kent D and Tremelling, Mark and Verspaget, Hein W and De Vos, Martine and Wijmenga, Cisca and Wilson, David C and Winkelmann, Juliane and Xavier, Ramnik J and Zeissig, Sebastian and Zhang, Bin and Zhang, Clarence K and Zhao, Hongyu and Silverberg, Mark S and Annese, Vito and Hakonarson, Hakon and Brant, Steven R and Radford-Smith, Graham and Mathew, Christopher G and Rioux, John D and Schadt, Eric E and Daly, Mark J and Franke, Andre and Parkes, Miles and Vermeire, Severine and Barrett, Jeffrey C and Cho, Judy H},
  issn         = {0028-0836},
  journal      = {NATURE},
  keyword      = {NETWORK,NUMBER,TUBERCULOSIS,MUTATIONS,HYPER-IGE SYNDROME,SUSCEPTIBILITY,RISK LOCI,METAANALYSIS,EXPRESSION},
  language     = {eng},
  number       = {7422},
  pages        = {119--124},
  title        = {Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease},
  url          = {http://dx.doi.org/10.1038/nature11582},
  volume       = {491},
  year         = {2012},
}

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