Major depressive disorder and irritable bowel syndrome risk: A Mendelian randomization study

by Guowei Sun, Yueyi Jiang

Previous studies have revealed a connection between major depressive disorder (MDD) and irritable bowel syndrome (IBS), but it remains obscure if the two diseases are related causally. Mendelian randomization was utilized in this investigation to ascertain whether MDD contributed to the emergence of IBS.

To examine possible connections between MDD and IBS, we used two-sample Mendelian randomization (MR) utilizing summary data from genome-wide association studies (GWAS). The Psychiatric Genomics Consortium (PGC) provided information on genetic associations with MDD (cases: 135,458; controls: 344,901). The Medical Research Council Integrative Epidemiology Unit (MRC-IEU) provided information on genetic associations with IBS (cases:10,939; controls:451,994). Inverse Variance Weighted (main analyses), MR-Egger regression, Weighted mode, and Weighted Median were the four MR methods used in this investigation. In addition, we also performed multiplicity and heterogeneity analyses to eliminate possible biases.

In the standard Inverse Variance Weighting (IVW) method, an increased risk of IBS was linked to a genetic susceptibility to MDD (OR: 1.01; 95% CI: 1.006 to 1.014, p = 1.02E-07). In addition, neither significant heterogeneity (IVW Q = 24.80, p = 0.73) nor horizontal pleiotropy (MR Egger p = 0.17; MRPRESSO p = 0.54) were detected in this MR analysis. The bidirectional analysis, however, did not show a genetic link between IBD and MDD (p steiger <0.01).

A direct causal relationship between MDD and IBS was revealed by Mendelian randomization study, which contributes to the effective clinical management of both diseases.