阿尔茨海默病和肌少症及体质量指数的关系:欧洲人群GWAS数据集分析  

Relationship between Alzheimer’s disease and sarcopenia and body mass index:analysis of GWAS datasets for European populations

作　　者：何启旺 陈波 梁复超 康泽伟 周原 季桉旭 唐夏林 He Qiwang;Chen Bo;Liang Fuchao;Kang Zewei;Zhou Yuan;Ji Anxu;Tang Xialin(Hubei University of Chinese Medicine,Wuhan 430061,Hubei Province,China;Hubei Provincial Hospital of Traditional Chinese Medicine,Affiliated Hospital of Hubei University of Chinese Medicine,Wuhan 430061,Hubei Province,China;Hubei Shizhen Laboratory,Wuhan 430061,Hubei Province,China;Xiangyang Central Hospital,Affiliated Hospital of Hubei University of Arts and Science,Xiangyang 441000,Hubei Province,China;Traditional Chinese Medical Hospital of Changxing,Huzhou 313100,Zhejiang Province,China)

机构地区：[1]湖北中医药大学,湖北省武汉市430061 [2]湖北省中医院,湖北中医药大学附属医院,湖北省武汉市430061 [3]湖北时珍实验室,湖北省武汉市430061 [4]襄阳市中心医院,湖北文理学院附属医院,湖北省襄阳市441000 [5]长兴县中医院,浙江省湖州市313100

出　　处：《中国组织工程研究》2026年第4期1036-1046,共11页Chinese Journal of Tissue Engineering Research

基　　金：湖北省自然科学基金青年项目(2022CFB923),项目负责人:唐夏林;湖北省中医药管理局青年人才项目(ZY2023Q001),项目负责人:唐夏林。

摘　　要：背景:阿尔茨海默病与肌少症相关,但因果关系尚未得到证实。探究老龄化人口中最常见的2个残疾负担疾病——阿尔茨海默病与肌少症的因果关系及可能的中介因素对进一步缓解国内老年人医疗保健成本与社会经济负担具有一定意义。目的:使用孟德尔随机化研究探索普通人群中阿尔茨海默病与肌少症之间的潜在因果关系,并探讨体质量指数在其中的作用。方法:采用基于公开的欧洲人群全基因组关联研究(GWAS)的双样本孟德尔随机化分析来推断因果关系,研究设计采用单变量孟德尔随机化和中介分析。通过综合流行病学单位(IEU)数据库,选择ieu-b-2作为阿尔茨海默病数据集(样本量为63 926),ieu-b-4816作为体质量指数数据集(样本量为99 998),ebi-a-GCST90000027作为四肢瘦体质量数据集(样本量为244 730),ukb-b-7478作为左手握力数据集(样本量为461026),ukb-b-10215作为右手握力数据集(样本量为461089),ukb-b-4711作为步行速度数据集(样本量为459915)。使用逆方差加权作为主要分析方法,并以多效性和异质性分析进行验证,采用Steiger方向性分析验证因果方向的合理性。结果与结论:(1)孟德尔随机化分析提供了阿尔茨海默病预测四肢瘦体质量风险(OR=1.009,95%CI:1.001-1.017,P=0.023)及步行速度(OR=1.010,95%CI:1.003-1.017,P=0.008)的证据,未观察到与握力的相关性;(2)阿尔茨海默病与体质量指数呈负相关(OR=0.893,95%CI:0.811-0.984,P=0.022);体质量指数与四肢瘦体质量呈正相关(OR=1.084,95%CI:1.031-1.141,P=0.002),与步行速度呈负相关(OR=0.975,95%CI:0.969-0.980,P <0.001);(3)中介分析表明阿尔茨海默病与和四肢瘦体质量及步行速度之间的因果关系部分由体质量指数介导,介导的比例分别为50.25%和32.11%;(4)结果表明基于大规模人群的遗传预测阿尔茨海默病是肌少症潜在的危险因素,且体质量指数在其中起到重要中介作用,这提示在临床�BACKGROUND:Alzheimer’s disease has been associated with sarcopenia,but a causal relationship has not been established.Exploring the causal relationship between the two most common disability-burdening diseases in the aging population-Alzheimer’s disease and sarcopenia-and their potential mediating factors holds certain implications for further alleviating the healthcare costs and socioeconomic burden for older adults in China.OBJECTIVE:To explore the potential causal relationship between Alzheimer’s disease and sarcopenia in the general population using a Mendelian randomization study and to explore the role of body mass index in this context.METHODS:Two-sample Mendelian randomization analysis based on published genome-wide association studies(GWAS)were used to infer causality,and univariate Mendelian randomization and mediation analyses were used in the study design.Through the Integrative Epidemiology Unit(IEU)database,ieu-b-2 was selected as the Alzheimer’s disease dataset(sample size:63926),ieu-b-4816 as the body mass index dataset(99998),ebi-a-GCST90000027 as the appendicular lean mass dataset(244730),ukb-b-7478 as the left hand grip strength dataset(461026),ukb-b-10215 as the right hand grip strength dataset(461089)and ukb-b-4711 as the walking pace dataset(459915).Inverse-variance weighting was used as the primary analysis method,and the results were validated by pleiotropy and heterogeneity analysis.The Steiger Directionality Test was performed to validate the reasonableness of the causal direction.RESULTS AND CONCLUSION:(1)The Mendelian randomization analyses provided evidence that Alzheimer’s disease predicted the risk of appendicular lean mass[odds ratio(OR)=1.009;95%confidence interval(CI),1.001-1.017;P=0.023),and walking pace(OR=1.010;95%CI,1.003-1.017;P=0.008).No correlation with hand grip strength was observed.(2)Alzheimer’s disease was negatively correlated with body mass index(OR=0.893;95%CI,0.811-0.984;P=0.022);body mass index was positively correlated with appendicular lean mass(OR=

关 键 词：阿尔茨海默病 体质量指数 肌少症 两步孟德尔随机化 中介分析 因果关联 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R749.16