Causal relationship between major depressive disorder, anxiety disorder and constipation: a two-sample Mendelian randomization study.

Background: Epidemiological and other studies have shown correlations among major depressive disorder (MDD), anxiety disorder (AXD) and constipation. However, no consensus has been reached regarding their interdependence and pathogenesis. Herein, we sought to further explore the causal associations between them.

Methods: Bidirectional two-sample Mendelian randomization (MR) analysis was performed to confirm the causal link between MDD, AXD and constipation. Genetic instrumental variables for MDD, AXD, and constipation were obtained from publicly available genome-wide association studies (GWASs). In this MR analysis, inverse variance weighting (IVW) was used as the primary analysis method to evaluate the causal effect. Additionally, we employed Cochran's Q test, MR‒Egger intercept and MR-PRESSO analysis to examine heterogeneity and pleiotropy. Moreover, leave-one-out analysis was employed to investigate the stability of the associations. Finally, a reverse analysis of Mendelian randomization was conducted.

Results: The results revealed a causal relationship between MDD and an increased risk of constipation (p = 0.0001), whereas AXD (p = 8.52 × 10^-1) did not increase the risk of constipation. In the inverse MR analysis, no causal associations were found (constipation to MDD: p = 9.37 × 10^-1; constipation to AXD: p = 8.51 × 10^-1).

Conclusion: This MR study revealed genetic evidence supporting a causal relationship between MDD and constipation.