Published: 07-02-2011 00:00 | Updated: 09-07-2014 10:55

29 new gene variants linked to ulcerative colitis

An international team of scientists, including researchers from Karolinska Institutet, have found 29 new regions in the genome that predispose to ulcerative colitis. The study identifies many candidate genes providing important insights into disease pathogenesis, and brings the tally of inflammatory bowel disease risk genes to 99.

"These rapidly increasing data help us to specifically define the genetic makeup of IBD and its major forms", says Associate Professor Mauro D'Amato at the Department of Biosciences and Nutrition, who led the Swedish part of the investigation. "It is our hope that this information may soon be exploited for a molecular classification of disease, especially in those cases where a differential diagnosis of Crohn's disease or ulcerative colitis cannot be established with current methods. However, the ultimate goal is of course to find new pharmaceutical targets for improved therapeutic strategies."

The findings, presented in the top-ranked journal Nature Genetics, stem from the analysis of more than 16,315 ulcerative colitis patients and 32,635 healthy controls from Europe, North America and Oceania. Similar to previous studies, the newly identified 29 genes appear to be involved in the control of inflammation and immune responses and in the maintenance of epithelial integrity in the intestinal mucosa.

Together with Crohn's disease, ulcerative colitis is one of the two major forms of chronic inflammatory bowel disease (IBD). Ulcerative colitis is a life-long disease leading to diarrhea and rectal bleeding, abdominal pain, weight loss and debility. Although medications can often keep at bay the disease, 10-20 percent of all affected individuals will undergo surgery to remove part or most of their colon.

All in all, the scientists have now identified 99 gene variants associated with inflammatory bowel disease. Associate Professor and Surgeon Leif Törkvist at the Department of Clinical Science Intervention and Technology, who also contributed to the study, is optimistic about the future implications of the findings: "These studies may lead to the early identification of patients genetically predisposed to more severe forms of disease or other difficult subtypes of ulcerative colitis, which is one of our toughest clinical challenges", he says.

The study was conducted within the frame of the International IBD Genetic Consortium (IIBDGC), with contributing researchers from 19 different countries, and corresponding authors are Associate Professor John Rioux from the Université de Montréal, Québec, Canada and Dr Carl Anderson from the Wellcome Trust Sanger Institute, Cambridge, UK.


Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.
Anderson C, Boucher G, Lees C, Franke A, D'Amato M, Taylor K, et al
Nat. Genet. 2011 Mar;43(3):246-52