Narrowing socioeconomic inequalities in coronary heart disease: insight from Mendelian randomization

Abstract Background Socioeconomic inequalities in coronary heart disease (CHD) represent a pressing global public health concern. However, which dimensions of socioeconomic status (SES) affect CHD and the potential modifiable mediators remain elusive. Methods We performed two-sample Mendelian randomization (MR) analyses based on summary data from large-scale genome-wide association studies in populations of European ancestry. Specifically, by applying bidirectional univariable MR (UVMR) and multivariable MR (MVMR), we investigated the causal relationships of education, occupation, income, Townsend deprivation index (TDI) with CHD and the independent effects of these SES indicators. We further employed a two-step MR to comprehensively profile the mediating effects of 23 behavioral, 3 psychological and 5 biological factors in the relationships. Results An independent causal association was observed between genetically predicated education and CHD, with a 30% lower risk of CHD (OR: 0.70; 95% CI: 0.53-0.93) for each 4.2-year of schooling. Each one-s.d. higher household income was causally, but not independently, associated with a 39% lower risk of CHD (OR: 0.61; 95% CI: 0.49-0.77). No significant causal association was suggested for occupation and TDI with CHD, and no reverse causal effect was observed for CHD on the SES indicators. Of 31 candidate mediators, nine factors mediated the effect of education on CHD significantly, with an individual mediation proportion of 33.5% for smoking, 29.2% for sedentary behaviour, 14.4% for blood lipids, 13.4% for BMI, 11.7% for systolic blood pressure, 9.5% for diastolic blood pressure, 7.8% for well-being spectrum, 6.4% for depression and 2.8% for blood glucose. Conclusions This study highlights that education was the primary SES indicator affecting CHD with considerable mediation by a number of modifiable risk factors. These findings inform policies to mitigate disparities of CHD risk attributable to socioeconomic inequalities. Key messages • Education can be prioritized over other common SES indicators as an essential strategy to reduce the burden of CHD. • Interventions for narrowing socioeconomic inequalities in CHD could focus on more easily modifiable mediating factors.