Andre Franke: "Host-microbe interactions shape genetic risk for inflammatory bowel disease"

Andre Franke

Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Germany

Host-microbe interactions shape genetic risk for inflammatory bowel disease

Crohn’s disease and ulcerative colitis are the two common forms of inflammatory bowel disease. Genome-wide association scans have implicated multiple susceptibility genes for these disorders, but an integrated view of the underlying biological pathways is lacking. We studied relevant pathways by undertaking a meta-analysis of Crohn’s disease and ulcerative colitis genome-wide association scans, with validation of significant findings in more than 75,000 cases and controls employing the custom “Immunochip”. We identify 71 new loci resulting in a total of 163 loci with genome-wide significance. Most loci contribute to both phenotypes and both directional and balancing selection effects are evident. We observe striking overlap between susceptibility loci for inflammatory bowel disease and mycobacterial infection. Gene expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to inflammatory bowel disease. Collectively, these findings shed light on the host-microbe interactions underlying this archetypal complex disease.