The causal relationship of human blood metabolites with the components of Sarcopenia: a two-sample Mendelian randomization analysis.

ABSTRACT

BACKGROUND: Sarcopenia is a progressive loss of muscle mass and function. Since skeletal muscle plays a critical role in metabolic homeostasis, identifying the relationship of blood metabolites with sarcopenia components would help understand the etiology of sarcopenia. METHODS: A two-sample Mendelian randomization study was conducted to examine the causal relationship of blood metabolites with the components of sarcopenia. Summary genetic association data for 309 known metabolites were obtained from the Twins UK cohort and KORA F4 study (7824 participants). The summary statistics for sarcopenia components [hand grip strength (HGS), walking pace (WP), and appendicular lean mass (ALM)] were obtained from the IEU Open GWAS project (461,089 participants). The inverse variance weighted method was used, and the MR-Egger, weighted median, and MR-PRESSO were used for the sensitivity analyses. Metabolic pathways analysis was further performed. RESULTS: Fifty-four metabolites associated with sarcopenia components were selected from 275 known metabolites pool. Metabolites that are causally linked to the sarcopenia components were mainly enriched in amino sugar and nucleotide sugar metabolism, galactose metabolism, fructose and mannose metabolism, carnitine synthesis, and biotin metabolism. The associations of pentadecanoate (150) with ALM, and 3-dehydrocarnitine and isovalerylcarnitine with HGS were significant after Bonferroni correction with a threshold of P < 1.82 × 10- 4 (0.05/275). Meanwhile, the association of hyodeoxycholate and glycine with the right HGS, and androsterone sulfate with ALM were significant in the sensitivity analyses. CONCLUSION: Blood metabolites from different metabolism pathways were causally related to the components of sarcopenia. These findings might benefit the understanding of the biological mechanisms of sarcopenia and targeted drugs development for muscle health.