Abstract
Assessing whether modifiable risk factors are causally associated with stroke risk is important in planning public health measures, but determining causality can be difficult in epidemiological data. We evaluated whether modifiable lifestyle factors including educational attainment, smoking, and body mass index are causal risk factors for ischemic stroke and its subtypes and hemorrhagic stroke. We performed 2-sample and multivariable Mendelian randomization to assess the causal effect of 12 lifestyle factors on risk of stroke and whether these effects are independent. Genetically predicted years of education was inversely associated with ischemic, large artery, and small vessel stroke, and intracerebral hemorrhage. Genetically predicted smoking, body mass index, and waist-hip ratio were associated with ischemic and large artery stroke. The effects of education, body mass index, and smoking on ischemic stroke were independent. Our findings support the hypothesis that reduced education and increased smoking and obesity increase risk of ischemic, large artery, and small vessel stroke, suggesting that lifestyle modifications addressing these risk factors will reduce stroke risk.
Highlights
AND PURPOSE: Assessing whether modifiable risk factors are causally associated with stroke risk is important in planning public health measures, but determining causality can be difficult in epidemiological data
Genetically predicted years of education was inversely associated with ischemic, large artery, and small vessel stroke, and intracerebral hemorrhage
GRAPHIC ABSTRACT: An online graphic abstract is available for this article
Summary
We performed 2-sample and multivariable Mendelian randomization to assess the causal effect of 12 lifestyle factors on risk of stroke and whether these effects are independent. AIS BMI CES ICH LAS MR OR SVS WHR any ischemic stroke body mass index cardioembolic stroke intracerebral hemorrhage large artery stroke Mendelian randomization odds ratio small vessel stroke waist-hip ratio. We performed a 2-sample MR analysis using summary statistics from the largest publicly available genome-wide association studies for educational attainment, sleep duration, physical activity, smoking, alcohol and coffee consumption, 4 dietary components, body mass index (BMI), and waist-hip ratio (WHR; Table I in the Data Supplement). For the stroke outcome measures, we obtained summary statistics from the MEGASTROKE Consortium,[3] consisting of 67 162 cases and 454 450 controls (n=60 341 ischemic stroke; 9006 cardioembolic stroke (CES); 6688 large artery stroke (LAS); 11 710 small vessel stroke [SVS]), which we restricted to Europeans since all the lifestyle traits genomewide association studies were conducted in Europeans.
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