The genetics of inflammatory bowel disease

Through rapid advances, genome-wide association studies (GWAS) have identified almost 100 susceptibility genes which confer an increased risk of developing inflammatory bowel disorders (IBD). This review focuses on recent advances in our understanding of the genetics of IBD. We discuss the role of key loci or genes in IBD pathophysiology. Some of the genes implicated have highlighted key pathways including bacterial recognition (NOD2), autophagy (ATG16L1, IRGM) in Crohn's disease. Other loci including CDH, HNF4A, LAMB1, and ECM1 are significantly associated with ulcerative colitis (UC) and have been linked to modulating epithelial barrier function. Nearly one-third of the described loci or genes are common to both Crohn's disease and ulcerative colitis. Several of these are involved in the IL23 signaling pathway (IL23R, IL12B, JAK2, and STAT3). These findings highlight the importance of genetic variability and its interactions with the immune system, gut microbiota, and environmental factors in determining pathogenesis of IBD.