Researchers identify gene linked to severe ulcerative colitis

Abdominal pain, diarrhea, and debilitating fatigue define the daily lives of millions of people worldwide who suffer from chronic bowel disease. Most of these individuals are diagnosed in their youth, and the disease’s progression can vary significantly, leaving patients uncertain about what the future holds. For some, ulcerative colitis is a manageable condition, while for others, it leads to frequent hospitalizations, complex medication regimens, and multiple surgeries.

Now, researchers from the Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT) at Aalborg University, have identified a genetic variant that may help predict which patients are likely to develop severe ulcerative colitis. Their study, just published in JAMA, could guide more targeted treatment strategies.

“We have long known about this gene and its connection to colitis. However, we have now demonstrated that the same gene can predict whether a patient will require more intensive treatment, including higher medication doses or major surgery. This knowledge is critical as we aim to tailor treatments more effectively,” says Ph.D. student and lead author, Marie Vibeke Vestergaard.

More aggressive treatment from the outset

The study, which analyzed both genetic data and Danish health records, found that around 3% of patients with ulcerative colitis carry a specific genetic variant—HLA-DRB1*01:03. Among this group, over 40% underwent major gastrointestinal surgery within the first three years of diagnosis—compared to only 9% of those without the variant.

“This is a group of patients who are especially hard-hit by the disease,” says Vestergaard.

“In cases of ulcerative colitis, early intervention is essential to prevent the disease from progressing and damaging the intestines. Our hope is that this discovery will allow doctors to closely monitor these patients from the very start, potentially administering more aggressive treatment early on.”

Vestergaard explains that preventing disease progression could not only improve patient outcomes but also reduce societal health care costs.

“By targeting treatment more precisely from the beginning, we can avoid the inefficiencies of trial-and-error approaches,” she adds.

A significant genetic effect

Head of Genomics at PREDICT, Associate Professor Aleksejs Sazonovs, was surprised by the strength of the findings, noting the substantial impact of a single genetic variant.

“I’m extremely proud of the work we’ve done at PREDICT, demonstrating how Denmark’s unique health data and biobank resources can benefit patients worldwide. As rates of inflammatory bowel diseases continue to rise in Western countries, the more we understand about the underlying genetics, the better we can treat and prevent these conditions,” says Sazonovs.

Sazonovs emphasized that while the results are promising, they must be validated through external studies. The next step will involve clinical trials to assess the impact of intensified monitoring and early treatment in patients with the genetic variant.