重庆医学2026，Vol.55Issue(6)：1255-1260,6.DOI:10.3969/j.issn.1671-8348.2026.06.009
睡眠昼夜节律异常与阿尔茨海默病发病风险因果关系的两样本孟德尔随机化研究
Two-Sample Mendelian randomization study on the causal relationship between sleep circadian rhythm dysfunction and risk of Alzheimer's disease
摘要
Abstract
Objective To evaluate the causal relationship between circadian dysfunction and Alzheimer's disease(AD)risk by using two-sample Mendelian randomization(MR)approach,employing genetic varia-tion as an instrumental variable.Methods The research data were obtained from the Genome-Wide Associa-tion Study(GWAS)database.Appropriate single nucleotide polymorphisms(SNP)were selected as instru-mental variables.Among the sleep circadian rhythm indicators,insomnia,daytime sleepiness,and sleep timing were the exposure factors,and AD was the outcome factor.Four analytical methods,namely inverse variance weighted(IVW)method,MR-Egger regression,weighted median method,and weighted estimation based on the mode,were used to evaluate the causal effect.Among them,the IVW method was the main analytical method,while the other three were auxiliary analytical methods for quality control.The reliability of the re-search results was evaluated through gene pleiotropy test,heterogeneity test,and sensitivity analysis.Results The IVW results indicated that there was a causal relationship between insomnia and AD(P<0.05),while daytime sleepiness(P=0.759)and sleep timing(P=0.789)did not have significant correla-tions with AD.Sensitivity analysis showed that the research results related to insomnia were stable.At the same time,the heterogeneity test results indicated that there was no significant heterogeneity among the in-strumental variables.According to the MR-Egger intercept test results,no gene pleiotropy was found among the instrumental variables.Based on the above statistical test analysis results,the results of this study have good robustness.Conclusion There is a clear causal relationship between insomnia and the risk of developing Alzheimer's disease.Insomnia increases the risk of Alzheimer's disease.However,no evidence has been found regarding the association between daytime sleepiness and sleep timing and the risk of Alzheimer's disease.关键词
阿尔茨海默病/昼夜节律/失眠/白天嗜睡/孟德尔随机化Key words
Alzheimer's disease/circadian rhythm/insomnia/daytime dozing/Mendelian randomization分类
医药卫生引用本文复制引用
宋际伟,张俊瑶,吴同轩,余乐,姚俊岩..睡眠昼夜节律异常与阿尔茨海默病发病风险因果关系的两样本孟德尔随机化研究[J].重庆医学,2026,55(6):1255-1260,6.基金项目
国家自然科学基金项目(82171183) （82171183）
上海市浦东新区卫生健康委员会医学人才培养项目(PWR12023-01). （PWR12023-01）
