Scientists have identified 71 new gene regions associated with inflammatory bowel disease (IBD), taking the total number of identified genes to 163. The findings indicate there is considerable overlap of genes associated with Crohn’s disease and ulcerative colitis, the two most common forms of IBD. The new genetic data, reported by an international team led by Wellcome Trust Sanger Institute investigators in the U.K., also suggest that many IBD loci are associated with other immune-mediated disorders, and in particular ankylosing spondylitis and psoriasis.
Crohn’s disease and ulcerative colitis affect over 2.5 million people of European ancestry, and prior genome-wide association studies have studied each disease separately. The Sanger-led team has now carried out a combined meta-analysis of Crohn’s disease and ulcerative colitis GWAS, and validated their disease-gene association findings in over 75,000 cases and controls. As well as identifying another 71 disease-related genes, the overall data indicated that 110 of the 163 loci are associated with both Crohn’s disease and ulcerative colitis. Moreover, 113 of the IBD loci are shared with other complex diseases or traits, “including 66 among the 154 loci previously associated with other immune-mediated diseases, which is 8.6 times the number that would be expected by chance,” state co-lead authors Luke Jostins, Ph.D., and Jeffrey Barrett, Ph.D.
Interestingly, there was a strong overlap between the IBD regions and genes that underly susceptibility to mycobacterial infections, and this finding supports a relationship between IBD risk and immune responses to bacterial infections, the investigators stress. “We see a genetic balancing act between defending against bacterial infection and attacking the body’s own cells,” Dr. Barrett comments. “Many of the regions we found are involved in sending out signals and responses to defend against bad bacteria. If these responses are over-activated, we found it can contribute to the inflammation that leads to IBD.”
Reporting in Nature, the authors admit that each of the genetic loci identified would have only a tiny individual impact on any person’s overall risk of developing IDB. However, the wealth of new genetic data generated will provide valuable insights about which biological pathways are involved, and in particular focus attention on the impact of microbial infections on mucosal immune system responses.
The team describes the findings in a paper titled “Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease.”