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Educational attainment as a modifier of the effect of polygenic scores for cardiovascular risk factors: cross-sectional and prospective analysis of UK Biobank

By Alice R Carter, Sean Harrison, Dipender Gill, George Davey Smith, Amy E Taylor, Laura D Howe, Neil M Davies

Posted 24 Mar 2021
medRxiv DOI: 10.1101/2021.03.16.21253723

Background: Understanding the interplay between educational attainment and genetic predictors of cardiovascular risk may improve our understanding of mechanisms relating educational attainment to cardiovascular disease. Methods: In up to 320 120 UK Biobank participants of White British ancestry (mean age = 57, female 54%), we created polygenic scores for nine cardiovascular risk factors or diseases: alcohol consumption, body mass index, low-density lipoprotein cholesterol, lifetime smoking behaviour, systolic blood pressure, atrial fibrillation, coronary heart disease, type 2 diabetes and stroke. We estimated whether educational attainment modified genetic susceptibility to these risk factors and diseases. Results: On the additive scale, higher educational attainment reduced genetic susceptibility to higher BMI, smoking, atrial fibrillation and type 2 diabetes, but increased genetic susceptibility to higher LDL-C and higher systolic blood pressure. On the multiplicative scale, there was evidence that higher educational attainment increased genetic susceptibility to atrial fibrillation and coronary heart disease, but no evidence of effect modification was found for all other considered traits. Conclusions: Educational attainment modifies the genetic susceptibility to some cardiovascular risk factors and diseases. The direction of this effect was mixed across traits considered and differences in associations between the effect of the polygenic score across strata of educational attainment was uniformly small. Therefore, any effect modification by education of genetic susceptibility to cardiovascular risk factors or diseases is unlikely to contribute substantially to the mechanisms driving inequalities in cardiovascular risk.

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