Repository logo

Smoking and stroke: A mendelian randomization study

Published version



Change log


Larsson, Susanna C 
Michaelsson, Karl 


Whether smoking is causally associated with risk of ischemic stroke and intracerebral hemorrhage is unknown. We used the Mendelian randomization design to explore the associations of genetic predisposition to smoking with ischemic stroke and its subtypes as well as intracerebral hemorrhage. Up to 372 single-nucleotide polymorphisms were used as instrumental variables for smoking initiation. We used summary statistics data for 438 847 individuals in the analyses of ischemic stroke (34 217 cases and 404 630 non-cases) and 3026 individuals in analyses of intracerebral hemorrhage (1545 cases and 1481 non-cases). Genetic predisposition to smoking initiation was statistically significantly positively associated with any ischemic stroke, large artery stroke, and small vessel stroke but not cardioembolic stroke or intracerebral hemorrhage. The odds ratios per one standard deviation higher log-odds of ever smoking regularly (smoking initiation) were 1.24 (95% CI 1.16-1.32; p = 1.310-10) for any ischemic stroke, 1.64 (95% CI 1.40-1.91; p = 2.810-10) for large artery stroke, 1.47 (95% CI 1.26-1.71; p = 1.110-6) for small vessel stroke, 1.12 (95% CI 0.99-1.27; p = 0.08) for cardioembolic stroke, and 1.13 (95% CI 0.81-1.58; p = 0.47) for intracerebral hemorrhage. This study provides genetic support for a causal association of smoking with ischemic stroke, particularly large artery and small vessel stroke.



32 Biomedical and Clinical Sciences, 3209 Neurosciences, 3202 Clinical Sciences, Tobacco, Neurosciences, Genetics, Stroke, Brain Disorders, Prevention, Tobacco Smoke and Health, Stroke, Cardiovascular, Cerebral Hemorrhage, Comorbidity, Databases, Genetic, Genetic Predisposition to Disease, Humans, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Smoking, Stroke, Sweden, White People

Journal Title


Conference Name

Journal ISSN


Volume Title



John Wiley & Sons Inc.
Wellcome Trust (204623/Z/16/Z)
British Heart Foundation (None)
Medical Research Council (MC_UU_00002/7)
British Heart Foundation (RG/18/13/33946)
his work was supported by the Swedish Research Council for Health, Working Life and Welfare (Forskningsrådet för hälsa, arbetsliv och välfärd) and the Swedish Research Council. S.B. is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 204623/Z/16/Z).