Rioux, J. D., Xavier, R. J., Taylor, K. D., Silverberg, M. S., Goyette, P., Huett, A. et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat. Genet. 39, 596-604

University of Toronto, Toronto, Ontario, Canada
Nature Genetics (Impact Factor: 29.35). 05/2007; 39(5):596-604. DOI: 10.1038/ng2032
Source: PubMed


We present a genome-wide association study of ileal Crohn disease and two independent replication studies that identify several new regions of association to Crohn disease. Specifically, in addition to the previously established CARD15 and IL23R associations, we identified strong and significantly replicated associations (combined P < 10(-10)) with an intergenic region on 10q21.1 and a coding variant in ATG16L1, the latter of which was also recently reported by another group. We also report strong associations with independent replication to variation in the genomic regions encoding PHOX2B, NCF4 and a predicted gene on 16q24.1 (FAM92B). Finally, we demonstrate that ATG16L1 is expressed in intestinal epithelial cell lines and that functional knockdown of this gene abrogates autophagy of Salmonella typhimurium. Together, these findings suggest that autophagy and host cell responses to intracellular microbes are involved in the pathogenesis of Crohn disease.

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Article: Rioux, J. D., Xavier, R. J., Taylor, K. D., Silverberg, M. S., Goyette, P., Huett, A. et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat. Genet. 39, 596-604

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    • "several autoimmune disorders, particularly in Crohn's disease of which inflammation plays a key role in its pathogenesis (Hampe et al., 2007; Parkes et al., 2007; Rioux et al., 2007; Cadwell et al., 2008; Gianchecchi et al., 2013). Autophagy has also been shown to protect against bacterial infections, such as Mycobacterium tuberculosis, Burkholderia cenocepacia, and adherent-invasive Escherichia coli (Abdulrahman et al., 2011; Castillo et al., 2012; Chargui et al., 2012). "
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