Causal association between depression and constipation: A bidirectional two-sample Mendelian randomization study

There is currently insufficient research on the causal relationship between depression and constipation. This study aims to provide clear evidence for the positive and negative causal relationship between depression and constipation through bidirectional two-sample Mendelian randomization (MR) analysis. MR is a statistical method used to evaluate the credible causal relationship between exposure and outcomes. In this study, we extracted corresponding genetic data from independent cohorts of patients with depression and constipation. Depression data was obtained from the Finngen database, while constipation data was obtained from the IEU OPEN genome-wide association study database. MR analysis was conducted using 5 methods: inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode. In addition, we also used Cochran Q test, MR-Egger intercept test, and leave-one-out analysis to test for the existence of horizontal pleiotropy and evaluate the robustness of MR analysis results. In the analysis of the impact of depression on constipation, we identified 15 significant and statistically strong single nucleotide polymorphisms, and the IVW random effects analysis showed a causal relationship (OR = 1.005 [1.003, 1.007], P = 1.26 × 10-5). When analyzing the impact of constipation on depression, 10 significant and statistically strong single nucleotide polymorphisms were identified, but IVW analysis did not find a causal relationship (OR = 73.768 [0.004, 1.306 × 10-6], P = .389). There is no heterogeneity in the impact of depression on constipation in the bidirectional analysis results, and there is heterogeneity in the impact of constipation on depression, but there is no horizontal pleiotropy. Our bidirectional two-sample MR analysis identified a causal relationship between depression and constipation. This discovery may help clinical doctors to intervene in depression patients in a timely and effective manner when treating constipation patients, avoiding further deterioration of the condition.