Genetic Links Found for Gastrointestinal Diseases

UPDATED: Nov. 10, 2012, at 12:01 a.m.

A study published recently in Nature found new genetic links between Crohn’s disease and ulcerative colitis, two autoimmune gut diseases that affect as many as 1.4 million people in the United States. The research was an immense collaborative effort, combining 75,000 data samples from 80 institutions including the Massachusetts General Hospital and Brigham and Women’s Hospital—both affiliated with Harvard Medical School—and the the Broad Institute.

“What this study shows is that by looking at genetic information for a large number of patients and controls you could map a genetic architecture of Crohn’s disease and colitis,” said Harvard Medical School Professor Ramnik Xavier, one of the study’s authors.“We used genome-wide association studies in combination with fine mapping tools ... to identify genetic factors that either increase or decrease the risk for developing these diseases.”

Crohn’s disease and colitis, collectively referred to as inflammatory bowel disease (IBD), both involve inflammation of the gastrointestinal tract. Colitis only affects the colon, while Crohn’s disease can affect any gastrointestinal area from the mouth to the anus.

Over the past decade, many genes related to Crohn’s and colitis have been discovered. Evidence for a genetic basis of the diseases was first uncovered in 2000. But in 2005, only two genes linked to the diseases had been determined. Now, 163 IBD loci, or genetic regions, are known--71 of which were identified in this study.

“When we examined the 163 loci that are associated with either disease, we found that many risk factors are shared between the two diseases, which much fewer unique factors for each disease,” said Xavier, who is also a senior associate member of the Broad Institute and Chief of Gastroenterology and Director of the Center for the Study of IBD at Massacusetts General Hospital.

With his lab’s own data, Xavier and his team were able to identify some pathways associated with the diseases but were unable to pinpoint the exact genes. But upon compiling the data from many different labs, the authors were able to identify the specific genes linked with these conditions.

From the 163 loci, the researchers found that some of the genes associated with IBD are also linked with risk of type 1 diabetes and psoriasis, a skin disease, suggesting that “there may be genetic elements targeting the immune system that might increase the risk of autoimmune diseases.”

Newly-discovered genetic predispositions for these diseases, such as those uncovered in this study, “point to novel clues in disease pathogenesis,” Xavier said, adding that “we now better appreciate the importance of innate immune responses and how...bacteria in the gut affect the diseases.”

He noted that genetic findings of this study also reveal information “about disease risk, onset, progression of disease, complications, and response to treatment” that will help scientists design personalized care for patients in the future.