Causal effect of sleep disorders on the risk of cerebrovascular events and complications： A two-sample Mendelian randomization study
10.19845/j.cnki.zfysjjbzz.2025.0165
- VernacularTitle:睡眠障碍对脑血管及其并发症风险的因果效应：一项双样本孟德尔随机化研究
- Author:
Jiajun XU
1
;
Yanhui PENG
1
Author Information
1. Department of Rehabilitation， The Sixth Affiliated Hospital of Xinjiang Medical University， Urumqi 830002， China
- Publication Type:Journal Article
- Keywords:
Sleep disorders;
Mendelian randomization;
Cerebrovascular outcomes;
Causal relationship;
Cerebral atherosclerosis
- From:
Journal of Apoplexy and Nervous Diseases
2025;42(10):890-900
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the causal association between sleep disorder-related phenotypes and cerebrovascular outcomes/complications using the two-sample Mendelian randomization （MR） method， and to determine causal orientation via directionality testing. Methods Genetic variations from genome-wide association studies were used as instrumental variables to analyze eight sleep-related phenotypes （continuous sleep， snoring， napping， insomnia， morning diurnal preference， daytime sleepiness， long sleep， and short sleep） against multiple cerebrovascular outcomes and complications （cerebral infarction， unruptured cerebral artery dissection， cerebral arteritis， cerebral amyloid angiopathy， unruptured cerebral aneurysm， cerebral atherosclerosis， intracerebral hemorrhage， vascular syndrome， and sequelae of cerebrovascular disease）. The inverse-variance weighted （IVW） method was used for primary analysis， with the assistance of the sensitivity methods such as MR-Egger， weighted median， simple mode， and weighted mode， and the Estimate value was used to characterized effect direction and magnitude， with statistical significance assessed by P value. The Steiger directionality test was used to compare the extent of variance explained by instrumental variables concerning exposure and outcome and confirm causal direction. Results The IVW analysis showed that snoring was associated with an increased risk of cerebral amyloid angiopathy （Estimate=8.08， 95% CI 1.93-14.23， P=0.01）， and long sleep duration was associated with an increased risk of cerebral atherosclerosis （Estimate=14.95， 95% CI 2.44-27.46， P=0.02）. Short sleep duration was associated with an increased risk of cerebral arteritis （Estimate=13.33， 95% CI 1.54-25.12， P=0.03）； however， inconsistent directions were observed across sensitivity methods （e.g.， MR-Egger）， and therefore， it was treated as suggestive evidence rather than a robust conclusion. The Steiger test showed R2exposure>R2outcome for most exposure-outcome pairs， and the key associations did not persist under reverse-direction analyses， supporting a forward causal pathway from sleep phenotypes to cerebrovascular outcomes and reducing the likelihood of reverse causation. Conclusion Genetic evidence supports a forward causal effect of sleep-related phenotypes on cerebrovascular outcomes and complications， with the most robust findings of “snoring increases the risk of cerebral amyloid angiopathy” and “long sleep duration increases the risk of cerebral atherosclerosis”. Identification and treatment of sleep-disordered breathing and avoidance of prolonged sleep may be used as potential targets for preventing cerebrovascular disease， and multi-ethnic prospective studies and interventional trials are needed to further validate these findings and clarify the underlying biological mechanisms.
