代谢物与肌少症的因果关系:来自欧洲人群的全基因组关联研究大数据分析  

Causal association between metabolites and sarcopenia:a big data analysis of genome-wide association studies in the European population

作　　者：陈佳永 唐梅玲 卢健棋[2] 庞延 杨尚冰 毛美玲 罗文宽 陆微 Chen Jiayong;Tang Meiling;Lu Jianqi;Pang Yan;Yang Shangbing;Mao Meiling;Luo Wenkuan;Lu Wei(Guangxi University of Chinese Medicine,Nanning 530200,Guangxi Zhuang Autonomous Region,China;First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530022,Guangxi Zhuang Autonomous Region,China)

机构地区：[1]广西中医药大学,广西壮族自治区南宁市530200 [2]广西中医药大学第一附属医院,广西壮族自治区南宁市530022

出　　处：《中国组织工程研究》2025年第29期6369-6380,共12页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金地区基金(82160887),项目负责人:卢健棋;广西自然科学基金项目(2021GXNSFBA196018),项目负责人:庞延,广西自然科学基金面上项目(2021GXNSFAA220111),项目负责人:卢健棋;国家中医临床研究基地业务建设第二批科研专项课题(JDZX2015146),项目负责人:卢健棋;国家中医药传承创新中心项目(2023019-10),项目负责人:卢健棋;广西岐黄学者培养项目(2024005-06-02),项目负责人:卢健棋;广西中医药管理局自筹经费科研课题(GXZYA20230065),项目负责人:庞延;广西高水平中医药重点学科-中医心病学(2024016-02-02),项目负责人:卢健棋。

摘　　要：背景:国内外研究均表明肌少症与代谢物有着紧密联系,目前最新的1400种血液代谢物与肌少症之间的联系尚不明确。目的:运用孟德尔随机化分析欧洲人群1400种代谢产物与肌少症之间存在的因果关系,进而预测相关代谢物在中国人群中的作用。方法:从OPEN GWAS网站获取欧洲人群肌少症相关特征(握力、四肢肌肉瘦体质量、步行速度)的全基因组关联研究(GWAS)数据作为结局数据。一项包含欧洲人群1400种代谢产物的GWAS作为暴露因素,选择与暴露因素显著相关的单核苷酸多态性作为工具变量。借助R软件(V4.3.2)的“TwoSampleMR”“gwasglue”等包对1400种代谢产物与肌少症之间存在的因果关联进行分析。研究的方法涉及逆方差加权法、MR-Eggeer回归截距、加权中位数法、简单模式等5种方法,并进行异质性、多效性、敏感性等验证分析,最后进行反向孟德尔随机化分析。结果与结论:①通过逆方差加权法分析欧洲人群1400种血清代谢产物与肌少症之间的因果关系,结果显示,1-亚油酰基-2-亚油酰基-GPC(18∶2/18∶3)、甘氨脱氧胆酸-3-硫酸酯是保护因素,随着代谢物的增加疾病的发病风险降低(P<0.01);②两种未知代谢物(X-12822、X-15486)和反式3,4-亚甲基庚酸酯是危险因素,随着两种未知代谢物(X-12822和X-15486)的增加,男性手握力低的程度随之增加;同样,随着反式3,4-亚甲基庚酸酯的增加,疾病发病风险也随之增加(P<0.01);③提示1-亚油酰基-2-亚油酰基-GPC(18∶2/18∶3)、甘氨脱氧胆酸-3-硫酸酯对肌少症具有抑制作用,两种未知代谢物(X-12822、X-15486)和反式3,4-亚甲基庚酸酯具有促肌少症的作用,这可能是未来肌少症研究和治疗的新思路、新依据,同时可为研究相关代谢物在中国人群中的作用提供参考依据。BACKGROUND:Studies at home and abroad have shown that sarcopenia is closely related to metabolites.At present,the relationship between the latest 1400 blood metabolites and sarcopenia is still unknown.OBJECTIVE:To analyze the causal relationship between 1400 metabolites and sarcopenia and its relevance with cardiovascular disease using Mendelian randomization.METHODS:Genome-wide association study(GWAS)data of sarcopenia-related characteristics(grip strength,limb muscle lean body mass,and walking speed)were obtained from the OPEN GWAS website as outcome data.A GWAS containing 1400 metabolites was used as an exposure factor,and single nucleotide polymorphisms significantly associated with exposure factors were selected as instrumental variables.The causal association between 1400 metabolites and sarcopenia was analyzed by“TwoSampleMR”and“gwasglue”packages of R software(V4.3.2).The research methods included inverse variance weighting,MREggeer regression intercept,weighted median method,and simple mode.Heterogeneity,pleiotropic,sensitivity and other verification analysis were performed.Finally,reverse Mendelian randomization analysis was performed.RESULTS AND CONCLUSION:(1)The causal relationship between 1400 serum metabolites and sarcopenia was analyzed by inverse variance weighting.The results showed that 1-linoleoyl-2-linoleoyl-GPC(18:2/18:3)and glycodeoxycholate 3-sulfate were protective factors,and the risk of disease decreased with the increase of metabolites(P<0.01).(2)Two unknown metabolites(X-12822 and X-15486)and trans-3,4-methyleneheptanoate were risk factors.With the increase of two unknown metabolites(X-12822 and X-15486),the degree of low grip strength of male hands increased.Similarly,with the increase of trans-3,4-methylene heptanoate,the risk of disease also increased(P<0.01).(3)To conclude,1-linoleoyl-2-linoleoyl-GPC(18:2/18:3)and glycodeoxycholate 3-sulfate have inhibitory effects on sarcopenia.Two unknown metabolites(X-12822 and X-15486)and trans-3,4-methyleneheptanoate can promote sarcope

关 键 词：代谢产物 肌少症 握力 步行速度 孟德尔随机化 因果关系 工程化组织构建 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R685