WSO - March 2023 - 346

1108272
WSO
International Journal of Stroke X(X)Du et al.
Research
Attention-deficit/hyperactivity disorder
and ischemic stroke: A Mendelian
randomization study
Runming Du1 , Yi Zhou1, Chong You2, Kevin Liu3,
Daniel A King4, Zhi-Sheng Liang1, Janice M Ranson5,
David J Llewellyn5,6, Jie Huang7 and Zhenyu Zhang1,8
Abstract
Background: Observational studies have found an association between attention-deficit/hyperactivity disorder (ADHD)
and ischemic stroke.
Aims: The purpose of this study was to investigate whether genetic liability to ADHD has a causal effect on ischemic
stroke and its subtypes.
Methods: In this two-sample Mendelian randomization (MR) study, genetic variants (nine single-nucleotide polymorphisms;
P < 5 × 10-8) using as instrumental variables for the analysis was obtained from a genome-wide association study
of ADHD with 19,099 cases and 34,194 controls. The outcome datasets for stroke and its subtypes were obtained from
the MEGASTROKE consortium, with 40,585 cases and 406,111 controls. MR inverse variance-weighted method was
conducted to investigate the effect of genetic liability to ADHD on ischemic stroke and its subtypes. Sensitivity analyses
(median-based methods, MR-Egger, MR-robust adjusted profile scores, MR-pleiotropy residual sum and outlier) were
also utilized to assess horizontal pleiotropy and remove outliers. Multivariable MR (MVMR) analyses were conducted to
explore potential mediators.
Results: Genetically determined ADHD (per 1 SD) was significantly associated with a higher risk of any ischemic stroke
(AIS) (odds ratio (OR) = 1.15, 95% confidence interval (CI) = 1.05-1.25, P = 0.002) and large-artery atherosclerotic stroke
(LAS) (OR = 1.40, 95% CI = 1.10-1.76, P = 0.005). The significant association was also found in sensitivity analyses and
MVMR analyses.
Conclusions: Genetic liability to ADHD was significantly associated with an increased risk of AIS, especially LAS. The
association between ADHD and LAS was independent of age of smoking initiation but mediated by coronary artery disease.
Keywords
Attention-deficit/hyperactivity disorder, ischemic stroke, Mendelian randomization
Received: 27 January 2022; accepted: 27 May 2022
1 Department of Global Health, Peking University School of Public Health, Beijing, China
2 Department of Biostatistics, Peking University School of Public Health, Beijing, China
3 Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
4 Northwell Health Cancer Institute and Feinstein Institute of Research, Lake Success, NY, USA
5 College of Medicine and Health, University of Exeter, Exeter, UK
6 Alan Turing Institute, London, UK
7 School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, Guangdong, China
8 Institute for Global Health and Development, Peking University, Beijing, China
Corresponding authors:
Jie Huang, School of Public Health and Emergency Management, Southern University of Science and Technology, 1088 Xueyuan Avenue, Shenzhen,
Guangdong, China.
Email: huangj@sustech.edu.cn
Zhenyu Zhang, Department of Global Health, Peking University School of Public Health, 38 Xueyuan Rd, Haidian District, 100191, Beijing, China.
Email: zzy@pku.edu.cn
International Journal of Stroke, 18(3)
https://doi.org/10.1177/17474930221108272
International Journal of Stroke
2023, Vol. 18(3) 346 -353
© 2022 World Stroke Organization
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DOI: 10.1177/17474930221108272
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