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OA
Two-Sample Mendelian randomization study on the causal relationship between sleep circadian rhythm dysfunction and risk of Alzheimer's disease
目的 利用两样本孟德尔随机化(MR)方法,以遗传变异作为工具变量,评估昼夜节律异常与阿尔茨海默病(AD)发病风险间的因果关系.方法 研究数据来自全基因组关联分析(GWAS)数据库,筛选合适的单核苷酸多态性(SNP)作为工具变量.睡眠昼夜节律指标中失眠、白天嗜睡和睡眠时型为暴露因素,以 AD为结局因素.采用逆方差加权(IVW)法、MR-Egger回归、加权中位数法和基于众数的加权估计这4种分析方法评估因果效应.其中,IVW 法作为主要分析方法,其余3种为辅助分析方法进行质量控制.通过基因多效性检验、异质性检验和敏感性分析评估研究结果的可靠性.结果 IVW 结果显示,失眠与 AD间存在因果关联(P<0.05),而白天嗜睡(P=0.759)和睡眠时型(P=0.789)与AD之间不存在明显关联.敏感性分析显示,失眠相关的研究结果具有稳定性.同时,异质性检验结果表明工具变量之间不存在明显的异质性.根据 MR-Egger截距检验结果,工具变量间未发现基因多效性.综合以上统计检验分析,表明结果具备较好的稳健性.结论 失眠与AD发病风险之间存在明显的因果关联,失眠会增加 AD的发病风险,然而尚未发现白天嗜睡和睡眠时型与AD发病风险之间的关联证据.
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.
宋际伟;张俊瑶;吴同轩;余乐;姚俊岩
南京医科大学上海东方临床医学院,上海 200120同济大学附属东方医院麻醉科,上海 200120同济大学附属东方医院麻醉科,上海 200120同济大学附属东方医院麻醉科,上海 200120南京医科大学上海东方临床医学院,上海 200120||同济大学附属东方医院麻醉科,上海 200120
医药卫生
阿尔茨海默病昼夜节律失眠白天嗜睡孟德尔随机化
Alzheimer's diseasecircadian rhythminsomniadaytime dozingMendelian randomization
《重庆医学》 2026 (6)
1255-1260,6
国家自然科学基金项目(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).
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