TOPLINE:

Patients with higher vs lower polygenic risk scores for susceptibility to inflammatory bowel disease (IBD) experienced more severe disease courses, including higher risks for hospitalizations and surgeries, and a greater need for advanced treatments early after diagnosis.

METHODOLOGY:

• Genetic risk factors for IBD are well known, but their role in predicting disease progression remains unclear. Researchers used nationwide Danish registry data and two cohorts to examine whether polygenic susceptibility to IBD was linked to disease course severity.
• They included patients with IBD, including Crohn’s disease (CD) and ulcerative colitis (UC), and matched them with control individuals without IBD.
• Susceptibility polygenic scores for CD and UC were calculated using genetic data from large genome-wide association studies and standardized to the population average.
• Researchers examined associations between susceptibility polygenic score and inflammatory markers (C-reactive protein [CRP], fecal calprotectin, and hemoglobin levels) at diagnosis and during follow-up intervals.
• Primary outcomes were: (1) time to IBD-related hospitalization exceeding 2 days, and (2) time to major IBD-related surgery. Other outcomes included medication use and a composite severity outcome assessed mainly within the first 3 years after diagnosis, with long-term follow-up.

TAKEAWAY:

• The analysis included 8267 patients with IBD and 9469 control individuals without IBD. Among those with IBD, 3732 had CD and 4535 had UC (mean age at diagnosis, 21.8 years and 23.3 years, respectively; 56% and 53% women, respectively).
• Each SD increase in susceptibility polygenic score was linked to significantly increased levels of fecal calprotectin (CD: beta coefficient, 0.27; UC: beta coefficient, 0.21) and decreased hemoglobin levels (CD: beta coefficient, -0.11; UC: beta coefficient, -0.08) and increased CRP levels only in patients with CD (beta coefficient, 0.15).
• Patients in the highest vs lowest quintile of susceptibility polygenic score had higher risks for major surgery in both the CD group (hazard ratio [HR], 2.74; 95% CI, 2.18-3.45) and the UC group (HR, 2.04; 95% CI, 1.55-2.69), with faster time to hospitalization (CD: HR, 1.81; 95% CI, 1.57-2.09; UC: HR, 1.69; 95% CI, 1.47-1.95).
• Each SD increase in the polygenic score was linked to 25% and 33% increased odds of severe disease in patients with CD and those with UC, respectively (P < .001 for both), and significantly increased use of biologics, immunomodulators, and corticosteroids. Disease extent partly explained this link in patients with CD but not in those with UC.

IN PRACTICE:

“Our findings of a dose-response relationship between the genetic burden of IBD susceptibility and disease severity provide a new biological understanding of disease severity,” the authors of the study wrote. 

SOURCE:

The study was jointly led by Marie Vibeke Vestergaard, PhD, and Kristine Højgaard Allin, MD, PhD, and Anne Krogh Nøhr, PhD, Aalborg University, Copenhagen, Denmark. It was published online in Gastroenterology.

LIMITATIONS:

The cohort was relatively young; thus, the results may not be applied to older patients. The study included only individuals of European ancestry, limiting generalizability. Some data were incomplete or inferred from registries, which may have introduced selection bias.

DISCLOSURES:

The study received funding from the Danish National Research Foundation, the Lundbeck Foundation, the Novo Nordisk Foundation, and the Colitis-Crohn Foreningen. One author reported consulting for Ferring and Pfizer. Two other authors reported receiving consultancy and/or speaker fees from various pharmaceutical and healthcare companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.