Abstract: OBJECTIVE: Studies at home and abroad have shown that sarcopenia (SP) is closely related to metabolites. At present, the relationship between the latest 1400 blood metabolites and sarcopenia is still unknown. In this study, Mendelian randomization (MR) was used to analyze the causal relationship between 1400 metabolites and sarcopenia and its correlation with cardiovascular disease. 
METHODS: Genome-wide association study (GWAS) data of sarcopenia-related characteristics (grip strength, limb muscle lean body mass, walking speed) were obtained from the open gwas website as outcome data. A GWAS containing 1400 metabolites was used as an exposure factor, and SNPs significantly associated with exposure factors were selected as instrumental variables (IV). The causal association between 1400 metabolites and sarcopenia was analyzed by ‘TwoSampleMR’ and ‘gwasglue’ packages of R software (V4.3.2). The research methods include inverse variance weighting (IVW), MR-Eggeer regression intercept, weighted median method (WM) and simple mode. Heterogeneity, pleiotropic, sensitivity and other verification analysis were performed. Finally, reverse MR analysis was performed.
RESULTS AND CONCLUSION: The causal relationship between serum metabolites and SP in 1400 was analyzed by IVW. 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). Two unknown metabolites (X-12822, 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). ‘1-linoleoyl-2-linoleoyl-GPC ( 18 : 2 / 18 : 3 )’ and ‘glycodeoxycholate 3-sulfate’ had inhibitory effects on SP. Two unknown metabolites (X-12822, X-15486) and ‘trans-3,4-methyleneheptanoate’ had SP-promoting effects. This may be a new idea and new basis for SP research and treatment in the future.

Key words: metabolites, sarcopenia, mendelian randomization, cardiovascular disease, causality