Causal Effects of Sleep Traits on Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study

Huan Cai,1,* Jialin Liang,2,* Zhonghua Liu,1 Liang Fang,1 Jinghong Zheng,3 Jiahe Xu,3 Liyi Chen,1 Wen Sun,4 Hao Zhang5 1Department of Rehabilitation, Zhongshan City People’s Hospital, Zhongshan 528403, Guangdong, People’s Republic of China; 2Department of Endocrinology and Metabo...

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Auteurs principaux: Cai H, Liang J, Liu Z, Fang L, Zheng J, Xu J, Chen L, Sun W, Zhang H
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Publié: Dove Medical Press 2020
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spelling oai:doaj.org-article:4dacd3dde3f047f483da18a803260c712021-12-02T13:06:45ZCausal Effects of Sleep Traits on Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study1179-1608https://doaj.org/article/4dacd3dde3f047f483da18a803260c712020-10-01T00:00:00Zhttps://www.dovepress.com/causal-effects-of-sleep-traits-on-ischemic-stroke-and-its-subtypes-a-m-peer-reviewed-article-NSShttps://doaj.org/toc/1179-1608Huan Cai,1,* Jialin Liang,2,* Zhonghua Liu,1 Liang Fang,1 Jinghong Zheng,3 Jiahe Xu,3 Liyi Chen,1 Wen Sun,4 Hao Zhang5 1Department of Rehabilitation, Zhongshan City People’s Hospital, Zhongshan 528403, Guangdong, People’s Republic of China; 2Department of Endocrinology and Metabolism, Zhongshan City People’s Hospital, Zhongshan 528403, Guangdong, People’s Republic of China; 3Department of Neurology, Zhongshan City People’s Hospital, Zhongshan 528403, Guangdong, People’s Republic of China; 4Division of Life Sciences and Medicine, Stroke Center and Department of Neurology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei 230026, Anhui, People’s Republic of China; 5Department of Neurology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hao ZhangDepartment of Neurology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, People’s Republic of ChinaTel +86-13450989238Fax +86 760-87727692Email zh_hao_neurol@163.comZhonghua LiuDepartment of Rehabilitation, Zhongshan City People’s Hospital, Zhongshan 528403, Guangdong, People’s Republic of ChinaTel 86-13923308898Email zhonghua_reha@163.comBackground: Unfavorable sleep habits have been linked with ischemic stroke in observational studies, but the causality remains unclear. The aim of this study is to investigate the potential causal role of three sleep traits, including sleep duration, insomnia, and chronotype, in ischemic stroke and its subtypes.Methods: We conducted two-sample Mendelian randomization (MR) analysis using single nucleotide polymorphisms associated with sleep duration, insomnia, and chronotype as instruments to estimate causal associations with ischemic stroke and its subtypes, among 34,217 ischemic stroke cases and 406,111 controls from the MEGASTROKE consortium. Inverse-variance weighted method was used as the main analyses. Alternative MR methods and sensitivity analyses were further performed.Results: We found suggestive evidence that per doubling of genetic liability for short sleep duration (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.01– 1.58) and frequent insomnia symptoms (OR, 1.19; 95% CI, 1.00– 1.41) were associated with a modest increase in risk of large artery stroke (LAS) but not with small vessel stroke, cardioembolic stroke, or any ischemic stroke. The association of frequent insomnia symptoms with LAS was stronger after the exclusion of the outlier (OR, 1.25; 95% CI, 1.04– 1.50). No significant association was observed for chronotype with any ischemic stroke subtype. Results were overall robust to sensitivity analyses, and there was little evidence of horizontal pleiotropy.Conclusion: We provided suggestive evidence for a potential causal role of short sleep duration and insomnia symptoms in LAS. Future researches are required to investigate whether improved sleep habits could help to mitigate LAS risk.Keywords: sleep, large artery stroke, ischemic stroke, Mendelian randomizationCai HLiang JLiu ZFang LZheng JXu JChen LSun WZhang HDove Medical Pressarticlesleeplarge artery strokeischemic strokemendelian randomizationPsychiatryRC435-571Neurophysiology and neuropsychologyQP351-495ENNature and Science of Sleep, Vol Volume 12, Pp 783-790 (2020)
institution DOAJ
collection DOAJ
language EN
topic sleep
large artery stroke
ischemic stroke
mendelian randomization
Psychiatry
RC435-571
Neurophysiology and neuropsychology
QP351-495
spellingShingle sleep
large artery stroke
ischemic stroke
mendelian randomization
Psychiatry
RC435-571
Neurophysiology and neuropsychology
QP351-495
Cai H
Liang J
Liu Z
Fang L
Zheng J
Xu J
Chen L
Sun W
Zhang H
Causal Effects of Sleep Traits on Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study
description Huan Cai,1,* Jialin Liang,2,* Zhonghua Liu,1 Liang Fang,1 Jinghong Zheng,3 Jiahe Xu,3 Liyi Chen,1 Wen Sun,4 Hao Zhang5 1Department of Rehabilitation, Zhongshan City People’s Hospital, Zhongshan 528403, Guangdong, People’s Republic of China; 2Department of Endocrinology and Metabolism, Zhongshan City People’s Hospital, Zhongshan 528403, Guangdong, People’s Republic of China; 3Department of Neurology, Zhongshan City People’s Hospital, Zhongshan 528403, Guangdong, People’s Republic of China; 4Division of Life Sciences and Medicine, Stroke Center and Department of Neurology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei 230026, Anhui, People’s Republic of China; 5Department of Neurology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hao ZhangDepartment of Neurology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, People’s Republic of ChinaTel +86-13450989238Fax +86 760-87727692Email zh_hao_neurol@163.comZhonghua LiuDepartment of Rehabilitation, Zhongshan City People’s Hospital, Zhongshan 528403, Guangdong, People’s Republic of ChinaTel 86-13923308898Email zhonghua_reha@163.comBackground: Unfavorable sleep habits have been linked with ischemic stroke in observational studies, but the causality remains unclear. The aim of this study is to investigate the potential causal role of three sleep traits, including sleep duration, insomnia, and chronotype, in ischemic stroke and its subtypes.Methods: We conducted two-sample Mendelian randomization (MR) analysis using single nucleotide polymorphisms associated with sleep duration, insomnia, and chronotype as instruments to estimate causal associations with ischemic stroke and its subtypes, among 34,217 ischemic stroke cases and 406,111 controls from the MEGASTROKE consortium. Inverse-variance weighted method was used as the main analyses. Alternative MR methods and sensitivity analyses were further performed.Results: We found suggestive evidence that per doubling of genetic liability for short sleep duration (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.01– 1.58) and frequent insomnia symptoms (OR, 1.19; 95% CI, 1.00– 1.41) were associated with a modest increase in risk of large artery stroke (LAS) but not with small vessel stroke, cardioembolic stroke, or any ischemic stroke. The association of frequent insomnia symptoms with LAS was stronger after the exclusion of the outlier (OR, 1.25; 95% CI, 1.04– 1.50). No significant association was observed for chronotype with any ischemic stroke subtype. Results were overall robust to sensitivity analyses, and there was little evidence of horizontal pleiotropy.Conclusion: We provided suggestive evidence for a potential causal role of short sleep duration and insomnia symptoms in LAS. Future researches are required to investigate whether improved sleep habits could help to mitigate LAS risk.Keywords: sleep, large artery stroke, ischemic stroke, Mendelian randomization
format article
author Cai H
Liang J
Liu Z
Fang L
Zheng J
Xu J
Chen L
Sun W
Zhang H
author_facet Cai H
Liang J
Liu Z
Fang L
Zheng J
Xu J
Chen L
Sun W
Zhang H
author_sort Cai H
title Causal Effects of Sleep Traits on Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study
title_short Causal Effects of Sleep Traits on Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study
title_full Causal Effects of Sleep Traits on Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study
title_fullStr Causal Effects of Sleep Traits on Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study
title_full_unstemmed Causal Effects of Sleep Traits on Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study
title_sort causal effects of sleep traits on ischemic stroke and its subtypes: a mendelian randomization study
publisher Dove Medical Press
publishDate 2020
url https://doaj.org/article/4dacd3dde3f047f483da18a803260c71
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