Genetics of ulcerative colitis

While it has been known for several decades that susceptibility to ulcerative colitis (UC), one of the two major forms of inflammatory bowel disease (IBD), is in part inherited, it is only recently that considerable progress has been made in identifying some of the key genetic determinants playing a role in predisposition to disease. The advent of genome-wide association studies (GWAS) has provided geneticists with an extremely powerful tool for the identification of causative genes in complex diseases. To date, 163 IBD risk loci have been identified, and functional insight obtained from genes mapping to these associated regions has highlighted the importance of immune function and gut interaction with bacteria, as well as the maintenance of epithelial barrier in UC pathogenesis. The functional characterization of the remaining genes, as well as the identification of rare causative variants in these associated regions, represents a considerable challenge for the future, but promises to unravel novel biological pathways that may be amenable to exploitation for the design of innovative therapeutic strategies in UC.