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

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.

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.

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).

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.