Understanding the consequences of education inequality on cardiovascular disease: mendelian randomisation study

Abstract

ObjectivesTo investigate the role of body mass index (BMI), systolic blood pressure, and smoking behaviour in explaining the effect of education on the risk of cardiovascular disease outcomes.DesignMendelian randomisation study.SettingUK Biobank and international genome-wide association study data.ParticipantsPredominantly participants of European ancestry.ExposureEducational attainment, BMI, systolic blood pressure, and smoking behaviour in observational analysis, and randomly allocated genetic variants to instrument these traits in mendelian randomisation.Main outcomes measureThe risk of coronary heart disease, stroke, myocardial infarction, and cardiovascular disease (all subtypes; all measured in odds ratio), and the degree to which this is mediated through BMI, systolic blood pressure, and smoking behaviour respectively.ResultsEach additional standard deviation of education (3.6 years) was associated with a 13% lower risk of coronary heart disease (odds ratio 0.86, 95% confidence interval 0.84 to 0.89) in observational analysis and a 37% lower risk (0.63, 0.60 to 0.67) in mendelian randomisation analysis. As a proportion of the total risk reduction, BMI was estimated to mediate 15% (95% confidence interval 13% to 17%) and 18% (14% to 23%) in the observational and mendelian randomisation estimates, respectively. Corresponding estimates were 11% (9% to 13%) and 21% (15% to 27%) for systolic blood pressure and 19% (15% to 22%) and 34% (17% to 50%) for smoking behaviour. All three risk factors combined were estimated to mediate 42% (36% to 48%) and 36% (5% to 68%) of the effect of education on coronary heart disease in observational and mendelian randomisation analyses, respectively. Similar results were obtained when investigating the risk of stroke, myocardial infarction, and cardiovascular disease.ConclusionsBMI, systolic blood pressure, and smoking behaviour mediate a substantial proportion of the protective effect of education on the risk of cardiovascular outcomes and intervening on these would lead to reductions in cases of cardiovascular disease attributable to lower levels of education. However, more than half of the protective effect of education remains unexplained and requires further investigation.

Mendelian Randomization Study of Obesity and Cerebrovascular Disease

“…SBP genetic association data were derived from the UK Biobank. Specifics of the analysis have been detailed elsewhere . Briefly, 317,195 individuals of European ancestry were included to generate summary level GWAS data for SBP corrected for the effects of antihypertensive treatment.…”

“…Genotyping and bioinformatic genetic analysis of each of these GWAS followed standardized procedures that are harmonized and comparable across the studies. Detailed genotype and phenotype assessment procedures have been previously published . Additional demographic and phenotypic information on the included studies is available in the Table.…”

“…Specifics of the analysis have been detailed elsewhere. 19 Briefly, 317,195 individuals of European ancestry were included to generate summary level GWAS data for SBP corrected for the effects of antihypertensive treatment. European ancestry-specific genome-wide meta-analysis summary statistics for association with HbA1c and FG were available through the latest effort of the Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC).…”

“…Detailed genotype and phenotype assessment procedures have been previously published. 8,9,11,[19][20][21] Additional demographic and phenotypic information on the included studies is available in the Table.…”

“…We finally divided the mediated effect by the total effect to estimate the proportion mediated, as previously reported. 19,32 The described method was applied to HbA1c as well.…”