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

BackgroundUnderstanding the interplay between educational attainment and genetic predictors of cardiovascular risk may improve our understanding of mechanisms relating educational attainment to cardiovascular disease. MethodsIn 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. ResultsOn 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. ConclusionsEducational 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. Key MessagesO_LIThe role of educational attainment in modifying the effect of polygenic scores for a wide range of cardiovascular risk factors or diseases has not previously been studied C_LIO_LIWe explore whether educational attainment modifies the effects of polygenic susceptibility to 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 C_LIO_LIEffect modification by education was observed for some cardiovascular polygenic scores, but not all. C_LIO_LIEffects were not always in the hypothesised direction and were dependent on the scale of analysis. C_LIO_LIModification of the effect of genetic susceptibility to cardiovascular risk factors or cardiovascular disease by educational attainment is unlikely to contribute substantially to the mechanisms driving inequalities in cardiovascular risk. C_LI