睡眠与衰弱的孟德尔随机化研究

Association between sleep and frailty:a Mendelian randomization study

目的 采用两样本双向孟德尔随机化(MR)方法分析睡眠与衰弱的关联,为衰弱的预防和干预提供依据。方法 睡眠时间、失眠和清晨型睡眠相关单核苷酸多态性(SNP)资料来自全基因组关联研究(GWAS)或GWAS Meta分析,分别包含446 118、1 331 010和697 828名研究对象;衰弱采用衰弱指数评估,相关SNP资料来自一项包含175 226名研究对象的GWAS Meta分析。采用逆方差加权法进行双向MR分析,并采用加权中位数法、最大似然比法、MR-Egger回归法和MR-PRESSO检验法进行敏感性分析。结果 正向MR分析结果显示,较长的睡眠时间(β=-0.170,95%CI:-0.255~-0.085)、清晨型睡眠(β=-0.036,95%CI:-0.058~-0.014)可能降低衰弱风险;失眠可能增加衰弱风险(β=0.167,95%CI:0.149~0.184)。反向MR分析结果显示,衰弱可能增加失眠风险(OR=1.645,95%CI:1.278~2.117)。双向MR分析结果均具有稳健性,并可排除异质性、水平多效性产生的影响。结论 睡眠时间、失眠、清晨型睡眠与衰弱存在因果关系。

Objective To examine the association between sleep and frailty using the bidirectional two-sample Mende⁃lian randomization(MR)approach,so as to provide the basis for the prevention and intervention of frailty.Methods The data on single nucleotide polymorphisms(SNP)related to sleep duration,insomnia and morning chronotype were col⁃lected from genome-wide association studies(GWAS)and meta-analysis of GWAS,involving 446118,1331010 and 697828 participants,respectively.The frailty was evaluated using the frailty index,and the relevant SNP data were col⁃lected from a meta-analysis of GWAS involving 175226 participants.A bidirectional MR analysis was performed using the inverse-variance weighted method.Sensitivity analyses employed the weighted median method,the maximum likeli⁃hood-based method,the MR-Egger regression,and the MR-PRESSO test.Results Forward MR analysis showed that longer sleep duration(β=-0.170,95%CI:-0.255 to-0.085)and morning chronotype(β=-0.036,95%CI:-0.058 to-0.014)decreased the risk of frailty,while insomnia increased the risk of frailty(β=0.167,95%CI:0.149-0.184).Re⁃verse MR analysis showed that frailty increased the risk of insomnia(OR=1.645,95%CI:1.278-2.117).Both bidirection⁃al MR results were robust,which excluded the impact of heterogeneity and horizontal pleiotropy.Conclusion Sleep du⁃ration,insomnia,and morning chronotype are associated with frailty.