中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (29): 6369-6380.doi: 10.12307/2025.715

• 组织构建相关数据分析 Date analysis of organization construction • 上一篇    

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

陈佳永1，唐梅玲2，卢健棋2，庞  延2，杨尚冰1，毛美玲1，罗文宽1，陆  微1   

  1. 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
  • 收稿日期:2024-07-08 接受日期:2024-09-24 出版日期:2025-10-18 发布日期:2025-03-10
  • 通讯作者: 卢健棋，教授，博士生导师，博士后合作导师，广西岐黄学者，广西中医药大学第一附属医院，广西壮族自治区南宁市 530022
  • 作者简介:陈佳永，1995年生，广西中医药大学在读硕士，主要从事心系病证防治研究。 并列第一作者：唐梅玲，主治医师，主要从事中医药防治心血管疾病方面的研究。
  • 基金资助:
    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；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；广西自然科学基金面上项目(2021GXNSFAA220111)，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

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

Chen Jiayong1, Tang Meiling2, Lu Jianqi2, Pang Yan2, Yang Shangbing1, Mao Meiling1, Luo Wenkuan1, Lu Wei1   

  1. 1Guangxi University of Chinese Medicine, Nanning 530200, Guangxi Zhuang Autonomous Region, China; 2First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530022, Guangxi Zhuang Autonomous Region, China
    Chen Jiayong, Master candidate, Guangxi University of Chinese Medicine, Nanning 530200, Guangxi Zhuang Autonomous Region, China
  • Received:2024-07-08 Accepted:2024-09-24 Online:2025-10-18 Published:2025-03-10
  • Contact: Lu Jianqi, Professor, Doctoral supervisor, First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530022, Guangxi Zhuang Autonomous Region, China
  • About author:Tang Meiling, Attending physician, First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530022, Guangxi Zhuang Autonomous Region, China Chen Jiayong and Tang Meiling contributed equally to this article.
  • Supported by:
    National Natural Science Foundation of China (Regional Fund), No. 82160887 (to LJQ); Guangxi Natural Science Foundation, No. 2021GXNSFBA196018 (to PY); The Second Batch of Scientific Research Special Projects for the Operational Construction of the National Clinical Research Base of Traditional Chinese Medicine, No. JDZX2015146 (to LJQ); National TCM Inheritance Innovation Center Project, No. 2023019-10 (to LJQ); Guangxi Qihuang Scholars Cultivation Project, No. 2024005-06-02 (to LJQ); Guangxi Natural Science Foundation (General Program), No. 2021GXNSFAA220111 (to LJQ); Guangxi Administration of Traditional Chinese Medicine Self-financed Research Project, No. GXZYA20230065 (to PY); Guangxi High-level Key Discipline of Traditional Chinese Medicine - Cardiology of Traditional Chinese Medicine, No. 2024016-02-02 (to LJQ)

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摘要：


文题释义：
孟德尔随机化：是目前在流行病学研究中用来推断疾病因果关系的一种成熟的统计分析方法，该方法将遗传变异作为工具变量对暴露因素和结局之间存在的因果关系进行检验，与临床随机对照试验设计方案中的随机分组相类似。其优势在于遗传变异固有的稳定性能够克服潜在混杂因素和传统观察性研究的影响。
肌少症：是以进行性的全身性骨骼肌力量及质量下降、功能障碍为主要特征的退行性病变，通常随着年龄的增长而发生，严重危害老年人群的健康生活。

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1 400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1 400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1 400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1 400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1 400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。
https://orcid.org/0009-0004-1164-6031(陈佳永)

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

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

Abstract: 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 1 400 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 1 400 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 1 400 metabolites and sarcopenia was analyzed by “TwoSampleMR” and “gwasglue” packages of R software (V4.3.2). The research methods included inverse variance weighting, MR-Eggeer 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 1 400 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 sarcopenia. This may be a new idea and new basis for sarcopenia research and treatment in the future. This study will also provide a reference for the study of the role of related metabolites in the Chinese population.

Key words: metabolites, sarcopenia, grip strength, walking speed, Mendelian randomization, causality, engineered tissue construction

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