Independent Associations of Education, Intelligence, and Cognition With Hypertension and the Mediating Effects of Cardiometabolic Risk Factors: A Mendelian Randomization Study

Figures

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  Figure 1.. Overview of the study design. A, Study design. B, Mediator selection process in phase 2. This study consisted of 2 stages of analyses. In stage 1, we assessed the causal associations of education, intelligence, and cognition with hypertension (main outcome) and blood pressure (secondary outcome) using univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) to evaluate the overall and independent causal effects of each exposure on outcomes, respectively. For hypertension, the UVMR results suggested that all 3 exposures were causally associated with hypertension, while the MVMR results further indicated that only education had an independent causal effect on hypertension with mutual adjustment for intelligence and cognition. In stage 2, we first screened candidate mediators for the association between education and hypertension by stringent criteria, and then calculated their mediating effects using 2-step MR. BF% indicates body fat percentage; BMI, body mass index; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; MVPA, moderate to vigorous physical activity; TV, television; and WHR, waist-to-hip ratio.

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  Figure 2.. UVMR and MVMR estimates of the causal associations of education, intelligence, and cognition with hypertension and blood pressure. A, Hypertension. B, Blood pressure. Plots (bars) represent OR (95% CI) or β (95% CI). As for hypertension, red plots represent the univariable Mendelian randomization (UVMR) results, and blue plots represent the multivariable Mendelian randomization (MVMR) results, with light ones representing the results from FinnGen/UK Biobank and dark ones representing the pooled results. As for blood pressure, red plots represent the UVMR results and blue plots represent the MVMR results. OR indicates odds ratio.

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  Figure 3.. Mendelian randomization (MR) estimates of proportions mediated by mediators in the causal association between education and hypertension. Histograms (bars) represent the mediated proportions (95% CIs). Red plots represent the proportions mediated by adiposity traits, grey plot represents the proportion mediated by a mediator of stress-related traits, and blue plots represent the proportions mediated by lipids. BF% indicates body fat percentage; BMI, body mass index; HDL-C, high-density lipoprotein cholesterol; and WHR, waist-to-hip ratio.