Does educational attainment modify the causal relationship between adiposity and cardiovascular disease? A Mendelian randomization study

A greater risk of cardiovascular disease is associated with low educational attainment and high adiposity. Despite the correlation between low educational attainment and high adiposity, whether educational attainment mod-ifies the risk of CVD caused by high adiposity remains poorly understood. We investigated the effect of adiposity (body mass index [BMI] and waist-to-hip ratio adjusted for BMI [WHRadjBMI]) on incident CVD among in-dividuals with varying education levels, using associational and one-sample Mendelian randomization (MR) survival analyses. Data were collected from 2006 to 2021, and sample sizes were 254,281 (27,511 CVD cases) for BMI and 253,968 (27,458 CVD cases) for WHRadjBMI. In the associational model, a standard deviation (SD) higher BMI was associated with 19.81 (95% CI: 18.55-21.06) additional cases of incident CVD per 10,000 person-years for individuals with a secondary education, versus 32.96 (95% CI: 28.75-37.17) for those without. When university degree served as the education variable, education group differences attenuated, with 18.26 (95% CI: 16.37-20.15) cases from a one SD higher BMI for those with a university degree versus 23.18 [95% CI: 21.56-24.72] for those without. For the MR model, an SD higher BMI resulted in 11.75 (95% CI:-0.84-24.38) and 29.79 (95% CI: 17.20-42.44) additional cases of incident CVD per 10,000 person-years for individuals with versus without a university degree. WHRadjBMI exhibited no effect differences by education. While the asso-ciational model showed evidence of educational attainment modifying the relationship between adiposity and incident CVD, it does not modify the association between adiposity and incident CVD in the MR models. This suggests either less education does not cause greater risk of incident CVD from high adiposity, or MR models cannot detect the effect difference. The associational point estimates exist within the MR models' confidence intervals in all BMI analyses, so we cannot rule out the effect sizes in the associational models.