Association of educational attainment with hypertension and type-2 diabetes: A Mendelian randomization study

BACKGROUNDDue to the long time interval between exposure and outcome, it is difficult to infer the causal relationship between educational attainment (EA) and common chronic diseases. Therefore, we utilized Mendelian randomization (MR) to predict the causal relationships of EA with hypertension and type-2 diabetes (T2DM). METHODSA two-sample MR analysis was conducted using genome-wide association studies (GWASs) combined with inferential measurements. A GWAS meta-analysis including 1,131,881 European individuals was used to identify instruments for EA. Hypertension and T2DM data were obtained from a Finnish database. MR analyses were performed using inverse-variance weighted meta-analysis (IVW), weighted median regression, MR‒Egger regression, simple mode regression, weighted mode regression and the MR-Pleiotropy RESidual Sum and Outlier test. Sensitivity analyses were further performed using the leave-one-out method to test the robustness of our findings. RESULTSUsing the MR approach, our results showed that EA was significantly associated with a reduced risk of hypertension (OR = 0.63; P = 2.94 × 10−47; [95% CI: 0.59, 0.67]) and type-2 diabetes (OR = 0.59; P = 1.25 × 10−16; [95% CI: 0.52, 0.67]). CONCLUSIONSThis study showed that EA is causally linked to the risk of chronic diseases, including high blood pressure and T2DM. •Summary Overview of the paper: The long time interval between exposure and outcome makes it difficult to infer causality between education level and common chronic diseases. Therefore, this paper aims to predict the causal relationship between educational attainment (EA), hypertension, and type 2 diabetes mellitus (T2DM) based on whole-genome sequencing data.•Research methods of this paper: This study adopted the method of Mendelian randomization (MR). MR Infers causal relationships between exposure and outcomes, such as disease risk, by using modifiable risk factors, namely genetic variants associated with exposure, such as EA, as instrumental variables. Furthermore, genetic variants associated with exposure are randomly assigned at conception, and using genetic variants in educational attainment as instrumental variables allows us to predict the effect of educational attainment on chronic diseases while reducing confounding by environmental factors and avoiding bias due to reverse causality.•Research conclusions and meanings of the paper: Genetic evidence based on MR Methods suggests a causal effect of EA on hypertension and type 2