Genetic Testing Identifies High-Risk Patients with Inflammatory Bowel Disease

More than half a million people in the U.K. are estimated to live with these disorders, which cause inflammation and ulceration in the gut. Determining early which patients will progress to severe disease remains challenging. New findings demonstrate that a specific HLA-DRB1 marker is associated with more aggressive IBD.

Researchers at the Wellcome Sanger Institute, working with the Francis Crick Institute and the NIHR IBD BioResource, identified a combination of genetic variants within the HLA-DRB1 gene—collectively termed HLA-DRB1*01:03—linked to more severe disease across ulcerative colitis and Crohn’s disease. The team indicates that genetic testing for HLA-DRB1*01:03 could help identify patients predisposed to severe disease so they can be monitored more closely and considered for advanced therapies earlier. The work is described as the largest genetic study of IBD traits to date.

Investigators genetically analyzed samples from more than 43,000 patients recruited across more than 100 hospitals. They studied data from 43,762 individuals in the NIHR IBD BioResource and UK IBD Genetics Consortium, including 21,839 with Crohn’s disease and 21,923 with ulcerative colitis or unclassified IBD. HLA-DRB1*01:03 was present in approximately one in 20 IBD patients.

Carriers of HLA-DRB1*01:03 had increased rates of multiple severe outcomes. These included a greater likelihood of requiring removal of part or all of the colon in both ulcerative colitis and Crohn’s disease, as well as a higher prevalence of perianal disease. The analysis also found an increased need for advanced therapies among HLA-DRB1*01:03–positive patients.

The findings were published in The Lancet Gastroenterology & Hepatology on June 15, 2026. According to the authors, genetic testing could help identify IBD patients at higher risk so they can be monitored closely and offered advanced treatments earlier, and may also help identify those at lower risk where conventional treatments might be sufficient. The study involved the Wellcome Sanger Institute, the Francis Crick Institute, the NIHR IBD BioResource, and the UK IBD Genetics Consortium.

“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,” said Dr. Qian Zhang, first author at the Wellcome Sanger Institute.

“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,” stated Dr. Laura Fachal, co-senior author at the Wellcome Sanger Institute.

Related Links
Wellcome Sanger Institute
Francis Crick Institute