Mechanisms of inflammatory bowel diseases: Insights from human genetics and chemical biology.

Human genetics has proven remarkably productive in linking genetic variants to a wide variety of diseases. Discovery initiatives from medical and population genetics have been especially prolific in generating new leads that point to underlying mechanisms of immune-mediated inflammatory diseases. While synthesizing leads from genetics into a functional understanding of disease pathophysiology is gaining momentum, challenges and opportunities abound. Here, we review advancements from combined efforts in functional genomics and chemical biology to construct and dissect mechanisms of mucosal immunity based on the genetics of inflammatory bowel disease (IBD). Taken together, a framework is emerging for interpreting disease mechanisms and conceiving new therapeutic hypotheses.