Genetics of inflammatory bowel disease: beyond NOD2

Abstract

The study of the genetic underpinnings of inflammatory bowel disease has made great progress since the identification of NOD2 as a major susceptibility gene. Novel genotyping and sequencing technologies have led to the discovery of 242 common susceptibility loci, 45 of which have been fine-mapped to statistically conclusive causal variants; 50 genes associated with very-early-onset inflammatory disease have been identified. The evolving genetic architecture of inflammatory bowel disease has deepened our understanding of its pathogenesis through identification of major disease associated pathways-knowledge that has the potential to indicate novel drug targets or markers for personalised medicine. However, many causal variants have yet to be identified, and a large proportion of missing heritability still needs to be accounted for. In addition, the medical and scientific communities are probably not yet fully harnessing the power of these genetic discoveries.