Effect of Visceral Adipose Tissue on Major Depressive Disorder: A Mendelian Randomisation Research

Abstract

Aims: Visceral adipose tissue (VAT) is associated with major depressive disorder (MDD) in observational studies, but these findings are susceptible to confounding and reverse causation. This study employed a two-sample Mendelian randomisation (MR) approach to assess the causal relationship between VAT and MDD.

Methods: We selected 221 single nucleotide polymorphisms associated with VAT mass in 325,153 individuals of European ancestry from UK Biobank as instrumental variables. Summary-level genetic data for MDD (59,851 cases and 113,154 controls) were accessible from the Psychiatric Genomics Consortium database. Primary MR analysis used the inverse-variance weighted (IVW) method, with weighted median and MR-Egger approaches as sensitivity analyses. Additional tests, including MR-Pleiotropy RESidual Sum and Outlier (PRESSO) and leave-one-out analysis, were conducted to evaluate pleiotropy and robustness.

Results: Genetically predicted higher VAT was significantly associated with increased MDD risk (odds ratio (OR) 1.179, 95% confidence interval (CI) 1.082–1.285, p < 0.001) based on IVW analysis. Sensitivity analyses yielded consistent results (weighted median OR 1.269, 95% CI 1.139–1.414, p < 0.001; MR-Egger OR 1.330, 95% CI 1.023–1.728, p = 0.034). Heterogeneity was observed (Cochran's Q = 353.14, p < 0.001), with no evidence of horizontal pleiotropy (MR-Egger intercept p = 0.342).

Conclusion: Our findings supported a causal relationship between increased VAT mass and elevated MDD risk. These results suggested that reducing VAT may be a potential strategy for preventing or mitigating MDD.