Abstract

Observational studies report inverse associations between educational attainment and depression/anxiety risks, but confounding hinders causal inference. This study aimed to assess potential causal relationships using Mendelian randomization (MR). Two-sample MR analysis was conducted using genetic instruments for education, smoking, body mass index, and physical activity from published genome-wide association studies. Depression and anxiety data came from the UK Biobank ([UKB] 117,782 individuals) and FinnGen (215,644 individuals) cohorts. Inverse variance weighted regression determined associations between exposures and mental health outcomes. Increased educational attainment was causally associated with reduced risks of depression (odds ratio [OR] = 0.99 per year, 95% confidence interval [CI]: 0.990-0.996, P < .001) and anxiety (OR = 0.99, CI: 0.98-0.991, P < .001) in both cohorts. Smoking initiation conferred higher risks of depression (UKB OR = 1.05, CI: 1.03-1.06, P < .001; FinnGen OR = 1.20, CI: 1.10-1.32, P < .001) and anxiety (FinnGen only, OR = 1.10, CI: 1.01-1.21, P < .05). Likewise, maternal smoking history associated with greater depression (UKB OR = 1.15, CI: 1.10-1.35, P = .027) and anxiety susceptibility (FinnGen OR = 3.02, CI: 1.67-5.46, P = .011). Higher body mass index elevated depression risk in both cohorts. Physical activity showed no clear associations. This MR study provides evidence that education may causally reduce mental health disorder risk. Smoking, obesity, and low activity appear detrimentally linked to depression and anxiety. Improving access to education could offer effective strategies for lowering population psychiatric burden.

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