AimsAssessing whether modifiable risk factors are causally associated with reduced stroke risk is important in planning public health measures, but determining causality can be difficult in epidemiological data. Leveraging large-scale genetic data in a technique known as Mendelian randomisation, we aimed to determine whether modifiable lifestyle factors including educational attainment, smoking, and body mass index are causal risk factors for ischaemic stroke and its different subtypes and haemorrhagic stroke. Methods and ResultsWe performed two-sample and multivariable Mendelian randomization to assess the causal effect of twelve lifestyle factors on risk of stroke and whether these effects are independent. We found genetic predisposition to increased number of years of education to be inversely associated with ischaemic, large-artery, and small-vessel stroke, as well as with intracerebral haemorrhage. Genetic predisposition to ever smoking regularly, higher body mass index (BMI), and higher waist-hip ratio are also associated with ischaemic and large-artery stroke. Additionally, we found that the effects of education, BMI, and smoking on ischaemic stroke to be independent of each other. ConclusionGenetic predisposition to higher educational attainment can reduce the risk of ischaemic, large-artery, and small-vessel stroke, while genetic predisposition to smoking and higher anthropometry measures can increase the risk of these stroke subtypes. This suggests that lifestyle modification addressing these risk factors will reduce stroke risk.

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