摘要
背景:近年来,多项流行病学研究表明肌少症与认知障碍可能存在潜在的病理学联系,但由于传统观察性研究存在方法学局限及难以控制的混杂因素,二者在遗传层面的因果关系尚未得到充分证实。目的:采用孟德尔随机化方法系统分析欧洲人群中肌少症与认知障碍的因果关系及潜在发病机制。方法:基于英国生物样本库中肌少症相关表型(全身无脂肪质量、双手握力及步行速度)的全基因组关联分析汇总数据和IEU数据库中认知功能的全基因组关联分析汇总数据。通过严格的阈值筛选和连锁不平衡去除等质控步骤后,采用双向孟德尔随机化分析方法展开研究。正向分析以肌少症相关特征作为暴露因素,认知功能作为结局变量;反向分析则交换两者的因果关系方向。此次研究以逆方差加权法作为主要分析方法,并辅以加权中位数法、MR-Egger回归法和稳健调整轮廓评分法进行多重验证。为保障研究结果的稳健性,研究进一步开展了异质性检验和系列敏感性分析。结果与结论:①孟德尔随机化逆方差加权法正向因果分析结果显示,全身无脂肪质量(OR=1.091,95%CI:1.001-1.188,P=0.045)、左手握力(OR=1.283,95%CI:1.077-1.527,P=0.005)、右手握力(OR=1.220,95%CI:1.022-1.456,P=0.027)和步行速度(OR=3.069,95%CI:1.997-4.717,P<0.001)均与认知功能呈显著正相关;②反向因果分析结果显示,认知功能仅与步行速度存在显著正向因果关系(OR=1.023,95%CI:1.004-1.043,P=0.014),而与全身无脂肪质量、左右手握力等指标未发现显著关联;③敏感性分析显示研究存在一定异质性,但没有发现水平多效性。研究结果表明肌少症与认知障碍之间存在因果关系,提示肌少症可作为认知障碍的预测指标,为临床早期筛查提供理论依据。此次研究基于国际公共数据库开展分析,其结果为中国人群肌少症与认知障碍的关联研究提供了新的证据,对两种疾病的早期筛查和预防具有重要参考价值。
BACKGROUND:In recent years,multiple epidemiological studies have suggested a potential pathological link between sarcopenia and cognitive impairment.However,due to methodological limitations in traditional observational studies and difficulties in controlling confounding factors,their genetic-level causal relationship has not yet been fully elucidated.OBJECTIVE:To systematically analyze the causal relationship and underlying pathogenesis between sarcopenia and cognitive impairment in European populations using Mendelian randomization methods.METHODS:This study utilized genome-wide association study(GWAS)summary statistics for sarcopenia-related phenotypes(whole-body fat-free mass,hand grip strength,and walking pace)from the UK Biobank,as well as GWAS summary data for cognitive function from the IEU database.After stringent quality control steps,including threshold screening and linkage disequilibrium removal,a bidirectional Mendelian randomization analysis was conducted.The forward analysis treated sarcopenia-related traits as exposure factors and cognitive function as the outcome variable,while the reverse analysis swapped their causal directions.The inverse-variance weighted method served as the primary analytical approach,supplemented by the weighted median method,MR-Egger regression,and robust adjusted profile score for validation.To ensure the robustness of the findings,the study further performed heterogeneity tests and a series of sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the forward causal analysis using the inverse variance-weighted Mendelian randomization method indicated that total fat-free mass(odds ratio=1.091,95%confidence interval:1.001–1.188,P=0.045),left handgrip strength(odds ratio=1.283,95%confidence interval:1.077–1.527,P=0.005),right handgrip strength(odds ratio=1.220,95%confidence interval:1.022–1.456,P=0.027),and walking speed(odds ratio=3.069,95%confidence interval:1.997–4.717,P<0.001)were all significantly positively correlated with cognitive function.(2)The results of the reverse causal analysis showed that cognitive function was only significantly positively associated with walking speed(odds ratio=1.023,95%confidence interval:1.004–1.043,P=0.014),with no significant association found for total fat-free mass or handgrip strength.(3)Sensitivity analyses indicated some heterogeneity in the study;however,horizontal pleiotropy was not observed.Research findings demonstrate a causal relationship between sarcopenia and cognitive impairment,suggesting that sarcopenia may serve as a predictive indicator for cognitive impairment and providing a theoretical basis for early clinical screening.Furthermore,this study,based on an international public database,offers new evidence for the association between sarcopenia and cognitive impairment in the Chinese population,which holds significant reference value for the early screening and prevention of these two conditions.
作者
尹兴晓
彭皓
宋艳萍
姚娜
申震
蒋阳
陈红波
黄丽
宋粤逾
李艳琪
陈奇刚
Yin Xingxiao;Peng Hao;Song Yanping;Yao Na;Shen Zhen;Jiang Yang;Chen Hongbo;Huang Li;Song Yueyu;Li Yanqi;Chen Qigang(School of Physical Education,Yunnan Normal University,Kunming 650500,Yunnan Province,China;The Third Affiliated Hospital of Yunnan University of Chinese Medicine(Rehabilitation Department,Kunming Hospital of Traditional Chinese Medicine),Kunming 650011,Yunnan Province,China)
出处
《中国组织工程研究》
北大核心
2026年第28期7388-7395,共8页
Chinese Journal of Tissue Engineering Research
基金
国家自然科学基金项目(82360943),项目负责人:申震
云南省“兴滇英才支持计划”青年人才专项项目(XDYCQNRC-2022-0609),项目负责人:申震
云南省科学技术厅中医联合专项课题(202101AZ070001-257,202101AZ070001-123),项目负责人:申震
云南省科学技术厅基础研究专项课题(202201AU070120),项目负责人:申震。
关键词
肌少症
认知障碍
双向孟德尔随机化
因果关系
肌-脑轴
肌肉质量
步行速度
sarcopenia
cognitive impairment
bidirectional Mendelian randomization
causal relationship
muscle-brain axis
muscle mass
walking speed
