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

Abstract

Background

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

Acknowledgments

We gratefully thank the MEGASTROKE consortium, UK Biobank, HUNT, Partners Biobank, and the 23andMe studies for providing summary statistics data. All MEGASTROKE consortium authors are listed in the online supplementary. The MEGASTROKE project received funding from sources specified at http://www.megastroke.org/acknowledgments.html.

Disclosure

The authors report no conflicts of interest for this work.

Additional information

Funding

This study received the support of the Social Welfare Science and Technology Research Project of Zhongshan City (2018B1065) and National Natural Science Foundation of China (81501193).