Causal relationships of circulating amino acids with sarcopenia-related traits: A bidirectional Mendelian randomization study

Abstract

Background and aim

Recent studies have indicated a correlation between certain Amino acids (AAs) and sarcopenia. However, the exact causal relationship among these associations is still unclear. This study aims to elucidate the causal relationships between 20 types of AAs and the phenotypic characteristics associated with sarcopenia through Mendelian randomization (MR) analysis.

Methods and results

This MR study employed single nucleotide polymorphisms (SNPs) that were significantly associated with both AAs and the traits of sarcopenia as instrumental variables (IVs). The main method for estimating causal effects was the inverse-variance weighted (IVW) approach. To ensure the robustness of the findings, additional methods such as weighted median, weighted mode, and MR Egger regression were used. Sensitivity analyses included heterogeneity and pleiotropy tests. In this research, we discovered potential causal relationships between AAs and traits associated with sarcopenia. We not only found that AAs previously studied, such as Glutamine, Tyrosine, Glycine, and branched-chain amino acids, play positive roles in muscle metabolism. Additionally, our study identified the role of AAs previously neglected or not considered in earlier research, such as Alanine, Lysine, Cysteine, and Methionine, which exert potential effects on muscle metabolism and offer considerable research potential and value.

Conclusions

This MR study clarified the reciprocal effects between circulating levels of AAs and sarcopenia-related traits. These results indicate that AAs may be used as biomarkers for diagnosing sarcopenia or as intervention targets for its treatment in clinical practice.