Abstract

The association between major depressive disorder (MDD) and irritable bowel syndrome (IBS) has been found in observational research; however, the causative relationship between MDD and IBS remains uncertain. Using the two-sample Mendelian randomization (MR) approach, we attempted to examine the causal effect of MDD on IBS. Independent genetic variants for MDD identified by Howard etal. based on a genome-wide meta-analysis were selected for this study. Gene-Outcome associations for IBS were gathered from UK Biobank and FinnGen databases. The MR analysis included inverse variance weighted (IVW), MR-Egger regression, weighted median, weighted mode, and MR-PRESSO sensitivity analyses. FinnGen database subjected to inverse variance weighted (IVW) analysis revealed that MDD may be a risk factor for the development of IBS (OR = 1.356, 95% CI: 1.125-1.632, p = 0.0013). The same finding was reached in UK Biobank for IVW (OR = 1.011, 95% CI: 1.006-1.015, p = 3.18 × 10-7 ), MR-Egger progression (OR = 1.030, 95% CI: 1.008-1.051, p = 0.007), and weighted median (OR = 1.011, 95% CI: 1.005-1.016, p = 0.0001). Our findings supported a causal relationship between MDD and IBS, which may have implications for the clinical management of IBS in individuals with MDD.

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