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

BackgroundObservational studies have consistently found educational inequalities in cardiovascular disease risk. Mendelian randomisation 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 cardiovascular disease risk and serum lipid concentrations before and after accounting for family structure. MethodsThis study included 28 448 siblings from the Trondelag Health Study (HUNT), 27 040 siblings from UK Biobank, and >120 000 individuals from an international within-sibship genome-wide association study, predominantly of European ancestry. The exposure was educational attainment. The outcomes were cardiovascular disease risk and serum concentrations of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. Standard and within-sibship Mendelian randomisation were used. ResultsIn the summary data analysis, there was a 6% lower risk of cardiovascular disease (odds ratio 0.94, 95% confidence interval 0.92 to 0.96) for each additional standard deviation of educational attainment. This was consistent having accounted for family structure (odds ratio 0.96, 95% confidence interval 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-level analysis. ConclusionsThere is a protective effect of educational attainment on cardiovascular disease 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. KEY MESSAGESO_ST_ABSQuestionC_ST_ABSIs the direct causal effect of education on cardiovascular disease (CVD) risk and CVD risk factors indicated by conventional Mendelian randomisation (MR) biased by demography or dynastic effects? FindingsConsistent with conventional MR analyses, within-sibship MR indicated that higher educational attainment is protective CVD risk and beneficial for serum concentrations of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. ImportancePreviously reported beneficial effects of educational attainment on CVD risk and serum lipid concentrations are likely causal and not due to bias from demographic or dynastic effects.