Genetic marker may flag severe IBD earlier in some patients

by Wellcome Trust Sanger Institute

edited by Sadie Harley, reviewed by Robert Egan

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In the largest genetic study of inflammatory bowel disease (IBD) traits to date, researchers have identified a genetic marker associated with more severe ulcerative colitis and Crohn's disease—the major forms of IBD.

Researchers from the Wellcome Sanger Institute, the Francis Crick Institute and the NIHR IBD BioResource genetically analyzed samples from more than 43,000 patients from more than 100 hospitals.

For the first time, the team identified a combination of genetic variants within the HLA-DRB1 gene—known collectively as HLA-DRB1*01:03—associated with more severe disease in people living with IBD.

The results, published in The Lancet Gastroenterology & Hepatology, suggest that genetic testing could identify IBD patients at risk of severe disease, meaning they could be monitored more closely and given advanced therapies earlier.

Why severity matters in IBD

More than half a million people in the U.K. are estimated to be living with Crohn's disease and ulcerative colitis. These are painful, debilitating and lifelong conditions with no known cure that cause ulceration and inflammation in the gut.

Treatments for Crohn's disease and ulcerative colitis depend on how severe the symptoms are and how much of the gut is affected. Patients are given medicines that reduce inflammation in the gut, including immunosuppressants and monoclonal antibody therapies, and in more severe cases, surgery also may be required.

The course of disease in IBD is very unpredictable. Some patients experience mild symptoms, including diarrhea, cramps and fatigue, while others have frequent flareups or develop much more severe disease that significantly impairs their quality of life.

What the study found

To understand the role of genetics in IBD, Sanger Institute scientists and their collaborators studied data from 43,762 patients from the NIHR IBD BioResource and UK IBD Genetics Consortium—including 21,839 individuals with Crohn's disease and 21,923 individuals with ulcerative colitis or unclassified IBD.

The researchers found that HLA-DRB1*01:03 was present in approximately one in 20 IBD patients and associated with multiple severe outcomes. This included the need for removal of part or all of the colon in those with Crohn's disease and ulcerative colitis, as well as individuals with perianal disease—a condition affecting the skin and tissue around the anus. There also was an increased need for advanced therapies in patients positive for HLA-DRB1*01:03.

Genetic testing of patients to see if they carry this combination of genetic variants could help identify those who are predisposed to more severe IBD so that they can be monitored closely and given advanced treatments earlier.

Researchers see path to treatment

Dr. Qian Zhang, first author at the Wellcome Sanger Institute, said, "We have undertaken the largest genetic study of IBD traits to date, involving data from more than 43,000 patients. With this large cohort we were able to find that a combination of genetic variants known as HLA-DRB1*01:03 is linked to more severe disease, not only in ulcerative colitis patients, but also in those with Crohn's disease."

Dr. Laura Fachal, co-senior author at the Wellcome Sanger Institute, said, "We found that IBD patients with these genetic variants within the HLA-DRB1 gene had more severe disease, including colon surgeries or advanced treatments, sometimes earlier in their disease progression.

"Genetic testing to see if patients carry these genetic variants may in future help inform treatment decisions, potentially supporting earlier access to advanced treatments. It could also help identify those at a lower risk of severe disease, where conventional treatments might be sufficient."

Professor James Lee, co-senior author at the Francis Crick Institute, said, "IBD can look very different for different people, and we don't fully know why. Some patients experience mild symptoms, whereas others develop severe disease and require advanced treatments or surgery. This study brings us one step closer to personalized medicine, and to building predictors of disease severity in IBD patients.

"In the future, patients with an increased risk of severe disease could be given advanced treatments earlier, to help improve their quality of life."

Publication details

The Lancet Gastroenterology & Hepatology (2026). DOI: 10.1016/S2468-1253(26)00113-5

Journal information: The Lancet Gastroenterology & Hepatology

Key medical concepts

Inflammatory Bowel DiseasesGenetic TestingMonoclonal antibodies

Clinical categories

GastroenterologyClinical genetics Provided by Wellcome Trust Sanger Institute Who's behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →

Robert Egan

Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →

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