Education and cardiovascular disease: a within-family Mendelian randomization analysis

Abstract

Background: Observational studies have consistently found educational inequalities in cardiovascular disease (CVD) risk. Mendelian randomization (MR) analyses have suggested a direct causal effect of education; however, estimates may be biased by demography or dynastic effects. This study aimed to estimate the effects of educational attainment on CVD risk and serum lipid concentrations before and after accounting for family structure.

Methods: This study included 26 961 siblings from the Trøndelag Health Study (HUNT) and 23 640 siblings from UK Biobank, and used data on >120 000 individuals, predominantly of European ancestry, from a recent international within-sibship genome-wide association study. The exposure was educational attainment. The outcomes were CVD risk and serum concentrations of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. Standard and within-sibship MR analyses were used.

Results: In the summary data analysis, there was a 6% lower risk of CVD [odds ratio (OR) 0.94, 95% confidence interval (CI) 0.92 to 0.96] for each additional standard deviation of liability to educational attainment. This was consistent having accounted for family structure (OR 0.96, 95% CI 0.91 to 1.01). Educational attainment was also beneficially associated with each serum lipid concentration both before and after accounting for family structure. Results were broadly similar in the individual participant analysis.

Conclusion: There is a protective effect of educational attainment on CVD risk and a beneficial effect on serum lipid concentrations not due to familial factors shared by siblings, suggesting that increasing education may be beneficial for cardiovascular health.

Keywords: HUNT; Mendelian randomization; UK Biobank; cardiovascular disease; education; lipids; within-family.