Mental health as a mediator of the association between educational inequality and cardiovascular disease: A Mendelian randomisation study

Background: Education is inversely associated with cardiovascular disease. Several mediators of this have been established however a proportion of the protective effect remains unaccounted for. Mental health is a proposed mediator, but current evidence is mixed and subject to bias from confounding factors and reverse causation. Mendelian randomisation (MR) is an instrumental variable technique that uses genetic proxies for exposures and mediators to reduce such bias.

Methods and Results: We performed logistic regression and two-step MR analyses, using UK Biobank data and genetic summary statistics, to investigate whether educational attainment affects risk of mental health disorders. We then performed mediation analyses to explore whether mental health disorders mediate the association between educational attainment and cardiovascular risk. Higher levels of educational attainment were associated with reduced depression, anxiety, and cardiovascular disease in observational analyses [Odds Ratio (95% Confidence interval) 0.79 (0.77-0.81), 0.76 (0.73-0.79) and 0.75 (0.74-0.76) respectively], and MR analyses provided evidence of causality [OR (95% CI) 0.72 (0.67-0.77), 0.50 (0.42-0.59) and 0.62 (0.58-0.66) respectively]. Both anxiety and depression were associated with cardiovascular disease in observational analyses [OR (95% CI) 1.63 (1.49-1.79) and OR (95% CI) 1.70 (1.59-1.82) respectively] but only depression showed evidence of causality in the MR analyses [OR (95% CI) 1.09 (1.03-1.15)]. An estimated 2% of the total protective effect of education on cardiovascular disease was mediated by depression.

Conclusions: Higher levels of educational attainment protect against mental health disorders and reduced depression accounts for a small proportion of the total protective effect of education on cardiovascular disease.