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

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dc.contributor.authorJostins, L.
dc.contributor.authorAndrews, J.
dc.date.issued2012
dc.description.abstractCrohn’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.
dc.description.statementofresponsibilityLuke Jostins ... Jane M. Andrews ...
dc.identifier.citationNature, 2012; 491(7422):119-124
dc.identifier.doi10.1038/nature11582
dc.identifier.issn0028-0836
dc.identifier.issn1476-4687
dc.identifier.orcidAndrews, J. [0000-0001-7960-2650]
dc.identifier.urihttp://hdl.handle.net/2440/74608
dc.language.isoen
dc.publisherNature Publishing Group
dc.relation.grantDK062431
dc.relation.grantDK062422
dc.relation.grantDK062420
dc.relation.grantDK062432
dc.relation.grantDK062423
dc.relation.grantDK062413
dc.relation.grantDK076984
dc.relation.grantDK084554
dc.relation.grantDK062429
dc.relation.grantDK062429-S1
dc.relation.grantCA141743
dc.relation.grantDK83756
dc.relation.grantAI062773
dc.relation.grantDK043351
dc.relation.grantU01 DK062418
dc.rights© 2012 Macmillan Publishers Limited. All rights reserved
dc.source.urihttps://doi.org/10.1038/nature11582
dc.subjectGenetics
dc.subjectGenomics
dc.subjectDisease
dc.subjectMedical research
dc.subjectImmunology
dc.titleHost-microbe interactions have shaped the genetic architecture of inflammatory bowel disease
dc.typeJournal article
pubs.publication-statusPublished

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