ABSTRACT Background and Purpose Evidence regarding the association between vitamin E and depression is inconsistent. To address this uncertainty, we employed a two‐sample Mendelian randomization (MR) approach to evaluate the potential causal effect of vitamin E on depression risk. Methods Genetic associations for vitamin E and depression were obtained from large‐scale, publicly available genome‐wide association studies (GWAS). We applied five complementary MR methods: inverse‐variance weighted (IVW), MR‐Egger, weighted median, simple mode, and weighted mode, with IVW serving as the primary analysis. To evaluate the robustness of our findings, we performed sensitivity analyses including Cochran's Q test, the MR‐Egger intercept test, MR‐Pleiotropy Residual Sum and Outlier (MR‐PRESSO), and leave‐one‐out analyses. Results In total, nine single‐nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs). Across all MR methods, the odds ratios (ORs) were statistically non‐significant ( P > 0.05): IVW (OR = 3.67, 95% CI: 0.85–15.85, p = 0.082), MR‐Egger (OR = 28.77, 95% CI: 1.05–786.24, p = 0.087), weighted median (OR = 4.44, 95% CI: 0.73–6.97, p = 0.105), simple mode (OR = 1.29, 95% CI: 0.08–21.79, p = 0.866), and weighted mode (OR = 1.29, 95% CI: 0.08–21.84, p = 0.866). The robustness of these null findings was supported by subsequent sensitivity analyses. Conclusions The present MR analysis indicated that genetically predicted vitamin E was not causally associated with the risk of depression. However, a non‐linear association cannot be excluded and thus merits further investigation.
Zhao et al. (Fri,) studied this question.