Causality between major depressive disorder and functional dyspepsia: a two-sample Mendelian randomization study

Abstract

Background: To investigate the causal relationship between major depression and functional dyspepsia using two-sample Mendelian randomization.

Methods: Data for major depression and functional dyspepsia were obtained from genome-wide association studies. We selected Single Nucleotide Polymorphisms (SNPs) strongly associated with severe depression. Mendelian randomization analysis was conducted using methods such as Inverse-Variance Weighted (IVW), MR-Egger, and Weighted Median Estimator (WME). Sensitivity analysis was performed to assess the robustness of the results.

Results: A total of 31 eligible SNPs were identified as instrumental variables for major depression. IVW analysis indicated a positive causal relationship between the two conditions (β = 0.328; SE = 0.137; p = 0.017), suggesting that severe depression increases the risk of functional dyspepsia (OR = 1.389; 95% CI: 1.062-1.816). Sensitivity tests showed no evidence of heterogeneity or horizontal pleiotropy (p > 0.05).

Conclusion: MR analysis had shown that major depressive disorder is associated with an increased risk of functional dyspepsia.

Keywords: Mendelian randomization; causal relationship; disease risk; functional dyspepsia; major depressive disorder.

Figure 1

Three core assumptions of MR analysis (①: the correlation hypothesis; ②: the independence hypothesis; ③: the assumption of exclusivity).

Figure 2

Scatter plot of two-sample MR analysis.

Figure 3

Forest plot of two-sample MR analysis.

Figure 4

Funnel plot of heterogeneity test results in two-sample MR analysis.

Figure 5

Leave-One-Out sensitivity analysis results of two-sample MR analysis.