Abstract

Observational studies have reported a negative association between educational attainment and type 2 diabetes (T2D), but the causality remains largely unknown. The aim of this study is to investigate the potential causal effect of educational attainment on T2D and whether such an effect is independent of cognitive performance. We conducted two-sample Mendelian randomization (MR) analysis using genetic variants strongly associated with educational attainment and cognitive performance to estimate the causal associations with T2D, among 61,714 T2D cases and 593,952 controls. We also performed multivariable MR to explore the independent effects of educational attainment and cognitive performance on T2D risk. In univariable MR, we found evidence that genetically predicted higher educational attainment [odds ratio (OR) 0.53 per 1-standard deviation (SD) increase; 95% confidence interval (CI) 0.47-0.60] and cognitive performance (OR 0.79 per 1-SD increase; 95%CI 0.69-0.91) were related to decreased risk of T2D. Our further multivariable MR results suggested that more years of education led to a reduced likelihood of T2D independently of cognitive performance (OR 0.52; 95%CI 0.42-0.64). However, the protective effect of cognitive performance on T2D was attenuated once educational attainment was controlled for (OR 1.08; 95%CI 0.88-1.32). We provided evidence to suggest that educational attainment protects against T2D independently of cognitive performance, but does not support a negative causal association between cognitive performance and T2D independently of educational attainment. Education might represent a potential target for intervention to battle type 2 diabetes risk.

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