徐佳骏 1韩炜 1刘丽丹 1刘文萍 1艾丽菲热·阿不都热西提 1彭颜晖1
作者信息
- 1. 新疆医科大学第六附属医院神经内科,新疆 乌鲁木齐 830002
- 折叠
摘要
Abstract
Objective To investigate the causal association between sleep disorder-related phenotypes and cerebro-vascular 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 in-strumental 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 com-plications(cerebral infarction,unruptured cerebral artery dissection,cerebral arteritis,cerebral amyloid angiopathy,un-ruptured cerebral aneurysm,cerebral atherosclerosis,intracerebral hemorrhage,vascular syndrome,and sequelae of cere-brovascular 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 di-rectionality 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 associ-ated with an increased risk of cerebral atherosclerosis(Estimate=14.95,95%CI 2.44-27.46,P=0.02).Short sleep du-ration was associated with an increased risk of cerebral arteritis(Estimate=13.33,95%CI 1.54-25.12,P=0.03);how-ever,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 evi-dence 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 in-terventional trials are needed to further validate these findings and clarify the underlying biological mechanisms.关键词
睡眠障碍/孟德尔随机化/脑血管结局/因果关系/脑动脉硬化Key words
Sleep disorders/Mendelian randomization/Cerebrovascular outcomes/Causal relationship/Cerebral atherosclerosis分类
医药卫生
