Association of major depressive disorder and increased risk of irritable bowel syndrome: A population-based cohort study and a two-sample Mendelian randomization study in the UK biobank

To examine the association between depression and the risk of incident irritable bowel syndrome (IBS).We included 98,564 participants free of IBS in the UK biobank. Depression was defined by self-report and Hospital Episode Statistics. The main outcome was incident IBS. Cox proportional hazards regression models and two-sample mendelian randomization were performed to estimate the risk of incident IBS.Among 98,564 participants, 8770 (8.9 %) participants had a depression diagnosis at baseline. During a median of 12.9-year follow-up, 224 cases of incident IBS were identified in patients with depression (2.0 per 1000 person-years), compared with 1625 cases in reference individuals (1.5 per 1000 person-years). After adjustment, the hazard ratio of incident IBS associated with depression was 1.26 (95 % CI: 1.01-1.41). Sensitivity analysis indicated similar results. The two-sample mendelian randomization based on the inverse variance weighted method provided evidence for the harmful role of depression in an increased risk of IBS with an OR of 1.57 (95 % CI: 1.24-1.99).Depression was mainly measured by self-report online CIDI-SF in the current study, rather than the gold diagnostic criteria including clinical structured interview, which might lead to potential measurement error. Lifestyle behaviors might change during the long-term follow-up, and time-varying covariates (i.e., smoking and alcohol status) may bias the estimate.Depression is associated with an increased risk of incident IBS. Further studies are warranted to confirm the role of depression on incident IBS and elucidate the underlying mechanisms.