Gene-Gene Interactions in Inflammatory Bowel Disease: Biological and Clinical Implications

The results of recently completed genome-wide association studies have advanced knowledge of inflammatory bowel disease (IBD) genetics, including the identification of over 30 genes or loci associated with Crohn's disease (CD). The possibility of interactions between genes, referred to by the term epistasis, needs to be carefully considered as both genetic and functional studies in IBD move forward. We review a paper in this issue of the Journal that reports evidence of epistasis in CD, and we discuss important issues that arise when trying to determine whether there is indeed interaction between genes and what their potential implications for disease pathogenesis and clinical outcome might be.