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  • Host-microbe interactions have shaped the genetic architecture of inflammatorybowel disease
    Jostins, Luke ...
    Crohnʼs disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, withrising prevalence in other populations1. ... Genome-wide association studies and subsequent meta-analyses of these two diseases2, 3 as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy4, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases5. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohnʼs disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significantfindings, 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.
    Vir: Nature : the international weekly journal of science. - ISSN 0028-0836 (Vol. 491, no. 7422, 2012, str. 119-124)
    Vrsta gradiva - članek, sestavni del ; neleposlovje za odrasle
    Leto - 2012
    Jezik - angleški
    COBISS.SI-ID - 512230968
    DOI

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