Bowel disease may be defense ‘gone awry’

U. PITTSBURGH (US) — A new study has found 71 genomic regions associated with inflammatory bowel disease (IBD), and suggests that infection defense genes play a key role in the condition.

The results, published in the November 1 issue of Nature, increase the number of known IBD-associated genomic regions to 163.

Crohn’s disease and ulcerative colitis, both forms of IBD, affect as many as 1.4 million people in the United States alone, says Richard Duerr, professor of medicine at Pitt School of Medicine and one of 12 co-investigators who conceived, designed and managed the study.

Both conditions are characterized by chronic inflammation of the intestine, typically leading to diarrhea and abdominal pain, and sometimes rectal bleeding.


“This research was conducted to fill gaps in our understanding of the genetic predisposition and biological pathways leading to Crohn’s disease and ulcerative colitis,” says Duerr, who is also co-director and scientific director of the UPMC Inflammatory Bowel Disease Center.

“The unprecedented participation of a combined total of more than 75,000 IBD and control study subjects from 15 countries and the willingness of more than 100 scientists and physicians to collaborate and pool resources enabled the study’s success.”

The research team conducted an analysis of combined data from 15 large studies on the genetics of IBD, identifying more than 25,000 single nucleotide polymorphisms (SNPs) or genetic variations with at least suggestive evidence for association with either Crohn’s disease, ulcerative colitis, or both forms of IBD.

That information was followed up by collecting data from an additional set of more than 41,000 IBD and control samples at 11 centers around the world, including the University of Pittsburgh, to verify that 163 genomic regions, including 71 newly identified ones, are associated with IBD.

Seventy percent of the IBD-associated genomic regions also are home to genetic variants that are associated with other immune-mediated, chronic inflammatory diseases, particularly psoriasis and ankylosing spondylitis, the researchers note.

Also, the IBD-associated genomic regions are enriched with genes linked to immune deficiencies that increase susceptibility to certain infections. The study uncovered pathways shared between responses to mycobacterial infections, such as tuberculosis and leprosy, and those predisposing people to inflammatory bowel disease.

“It’s possible that the biological mechanisms intended to protect us from infection go awry and overreact, triggering inflammation that characterizes IBD,” Duerr notes.

The research team was co-led by Judy H. Cho of Yale University and Jeffrey Barrett of Wellcome Trust Sanger Institute, in the UK.

The project was funded in part by the National Institute of Diabetes and Digestive and Kidney Diseases, which is part of the National Institutes of Health, as well as the Crohn’s & Colitis Foundation of America and the International IBD Genetics Consortium.

Source: University of Pittsburgh