Chinese Journal of Tissue Engineering Research ›› 2025, Vol. 29 ›› Issue (29): 6369-6380.doi: 10.12307/2025.715

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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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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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