Intrinsic capacity, genetic susceptibility and incident inflammatory bowel disease: a prospective cohort study in UK Biobank

Abstract Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder, but whether intrinsic capacity (IC), a multidomain measure of functional reserve, is associated with incident IBD remains unclear. We analysed 427,489 UK Biobank participants free of IBD at baseline and examined associations of baseline IC deficit burden with incident IBD, Crohn’s disease (CD), and ulcerative colitis (UC), as well as joint effects with polygenic risk scores (PRS). During a median follow-up of 13.74 years, 3,719 participants developed IBD. Compared with participants with no IC deficits, those with 2, 3, and ≥ 4 deficits had progressively higher risks of incident IBD, and incidence rates increased from 0.556 to 1.067 per 1,000 person-years across IC categories. Associations were stronger for CD than for UC; participants with ≥ 4 deficits had hazard ratios of 2.44 for CD and 1.35 for UC. Poorer IC was most strongly associated with IBD among individuals with high PRS, with the highest risk observed for CD in those with both severe IC impairment and high PRS. These findings suggest that reduced IC is independently associated with increased IBD risk and may provide complementary information for risk stratification.