Genetically modulated educational attainment and coronary disease risk

Abstract

Aims: Genetic disposition and lifestyle factors are understood as independent components underlying the risk of multiple diseases. In this study, we aim to investigate the interplay between genetics, educational attainment-an important denominator of lifestyle-and coronary artery disease (CAD) risk.

Methods and results: Based on the effect sizes of 74 genetic variants associated with educational attainment, we calculated a 'genetic education score' in 13 080 cases and 14 471 controls and observed an inverse correlation between the score and risk of CAD [P = 1.52 × 10-8; odds ratio (OR) 0.79, 95% confidence interval (CI) 0.73-0.85 for the higher compared with the lowest score quintile]. We replicated in 146 514 individuals from UK Biobank (P = 1.85 × 10-6) and also found strong associations between the 'genetic education score' with 'modifiable' risk factors including smoking (P = 5.36 × 10-23), body mass index (BMI) (P = 1.66 × 10-30), and hypertension (P = 3.86 × 10-8). Interestingly, these associations were only modestly attenuated by adjustment for years spent in school. In contrast, a model adjusting for BMI and smoking abolished the association signal between the 'genetic education score' and CAD risk suggesting an intermediary role of these two risk factors. Mendelian randomization analyses performed with summary statistics from large genome-wide meta-analyses and sensitivity analysis using 1271 variants affecting educational attainment (OR 0.68 for the higher compared with the lowest score quintile; 95% CI 0.63-0.74; P = 3.99 × 10-21) further strengthened these findings.

Conclusion: Genetic variants known to affect educational attainment may have implications for a health-conscious lifestyle later in life and subsequently affect the risk of CAD.

Keywords: Atherosclerosis; Coronary artery disease; Genetics; Genome-wide association studies; School education.

Figure 1

‘Genetic education score’ and risk of coronary artery disease. A weighted genetic risk score based on 74 genetic variants affecting length of education reported by Okbay et al. (‘genetic education score’) was calculated in individuals from nine case–control studies for coronary artery disease (total n = 27 551). The calculation of the score is described in Methods section, and the description for these nine studies is provided in Supplementary material online, Text. Logistic regression was performed to evaluate the effect size of the weighted genetic risk score on the risk of coronary artery disease in each study separately and afterwards meta-analysis was performed to combine the effects across nine studies. Forest plot displays a consistent inverse correlation across studies between the ‘genetic education score’ and odds of coronary artery disease.

Figure 2

Inverse relationship of genetically determined educational attainment and risk of coronary artery disease. Individuals from each of the nine studies were grouped into quintiles based on their weighted genetic risk score for school attainment, with Quintile 1 indicating the lowest genetic score and Quintile 5 the highest. Odds ratios, shown with and 95% CIs, for coronary artery disease were 20.8% lower in the quintile with the highest genetically determined educational attainment when compared with those with the lowest ‘genetic education score’. The distribution of all cases (red bars) with coronary artery disease is decreasing with an increasing ‘genetic education score’, while that of all controls (blue bars) has an opposite trend. P = 7.66 × 10⁻⁹ was obtained from Cochran–Armitage trend test.

Take home figure

Interpretation of findings. Educational attainment is partially modulated by common genetic variants^, and inversely associated with cardiovascular diseases.^, In the present study, we have found that the common genetic variants that influence length of school education are also associated with cardiovascular risk factors and the manifestation of coronary artery disease. Importantly, the associations between genetic variants with coronary artery disease and its risk factors remained to be significant after adjustment for actual length of education. Thus, genetic factors may also influence decision-making for a health-conscious lifestyle later in life and affect the prevalence of coronary artery disease through its risk factors.