Could Polygenic Risk Score Indicate Risk of Primary Sclerosing Cholangitis in IBD?

Patients with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) had significantly higher polygenic risk score and provided evidence that IBD-PSC disease pathogenesis may be genetically distinct from IBD alone, a recent study published in BMJ Open Gastroenterology found.

The researchers included adults with a confirmed diagnosis of IBD from Mayo Clinic IBD cohort (Cohort 1) and Washington University IBD cohort (Cohort 2).

Of the 1130 patients with IBD, 63 patients (5.6%) had PSC. Among the 381 patients who had ulcerative colitis (UC), 12% had PSC. Among the 761 patients who had Crohn’s disease (CD), 1.4% had PSC.

Patients with PSC-IBD had significantly higher polygenic risk score than patients with only IBD.

Patients with IBD-PSC presented with a clinical course different from that of patients with IBD alone. Among patients with UC, those with UC-PSC were younger at age of diagnosis and with more extensive disease.

These findings may help “guide an individualized IBD management strategy and identify patients with the highest likelihood of developing PSC,” the study read. “Further research in discovering which specific molecular pathways influencing the differences is warranted.”

PSC is highly associated with IBD, especially UC. The prevalence of UC among patients with PSC ranges from 60% to 70%. Conversely, PSC affects about 7% of patients with UC.

“It is important for clinicians to identify which patients with IBD are more likely to have PSC, since this could significantly determine IBD disease behavior and clinical outcome and allow for a more personalized therapeutic approach,” the authors explained.

Reference:
Wang M, Friton JJ, Raffals LE et al. Polygenic risk score predicts risk of primary sclerosing cholangitis in inflammatory bowel disease. BMJ Open Gastroenterol. 2023:10;e001141. DOI: 10.1136/bmjgast-2023-001141