Associations of sleep patterns, Metabolic Dysfunction, and Genetic Susceptibility With Incident Crohn’s Disease and Ulcerative Colitis: A Prospective Cohort Study

Background Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder with rising global incidence, yet early-life risk stratification remains limited. Sleep disturbances, metabolic dysfunction, and genetic susceptibility have each been implicated in IBD development, but their combined effects have not been comprehensively evaluated in large prospective populations. Methods We conducted a prospective cohort study including participants from the UK Biobank without IBD at baseline. A multidimensional sleep pattern score was constructed using self-reported sleep behaviors. Metabolic dysfunction was assessed using the triglyceride–glucose (TyG) index, and genetic susceptibility was quantified using polygenic risk scores (PRS) for IBD. Cox proportional hazards models were used to examine associations with incident Crohn’s disease (CD) and ulcerative colitis (UC), with stratified and interaction analyses across risk dimensions. Results During follow-up, unfavorable sleep patterns were associated with a higher risk of incident IBD, independent of sociodemographic and lifestyle factors. Participants with both poor sleep patterns and elevated TyG index exhibited the highest risk of incident IBD. Moreover, individuals with adverse sleep patterns and high genetic susceptibility demonstrated a pronounced elevation in IBD risk compared with those at low genetic risk. These associations were consistent across sensitivity analyses. Conclusions This large prospective study demonstrates that sleep patterns, metabolic dysfunction, and genetic susceptibility jointly contribute to IBD risk. Integrating behavioral, metabolic, and genetic dimensions may enable improved population-level risk stratification and support early preventive strategies for IBD.