Assessing the causal association between human blood metabolites and grip strength：a mendelian randomization analysis

Abstract

Abstract Background Metabolic disturbance has been reported in patients with sarcopenia. However, evidence about the causal role of metabolites in preventing sarcopenia is lacking. Systematic investigations of the causal relationships between blood metabolites and sarcopenia could help to identify novel targets for sarcopenia screening and prevention. Methods We conducted univariate and multivariable mendelian randomization (MR) analysis. The data for 486 human blood metabolites were obtained from a genome‑wide association study (GWAS) comprising 7824 participants. The GWAS data for grip strength were obtained from the UK Biobank consortium. GWAS data for type 2 diabetes and obesity from the FinnGen consortium. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Results Univariate MR analysis revealed four metabolites with causal effects on grip strength [phenylalanylserine: Beta = 1.04, 95% CI = 1.02–1.06, P = 0.0004; hyodeoxycholate: Beta = 1.03, 95% CI = 1.01–1.05, P = 0.01; 3-dehydrocarnitine: Beta = 0.89, 95% CI = 0.83 − 0.6 = 96, P = 0.003; X-11440: Beta = 1.05, 95% CI = 1.03–1.07, P = 0.00003]. However, after the multivariable MR analysis, only phenylalanylserine remained significantly associated with grip strength. Conclusions The phenylalanylserine is causatively associated with grip strength. The results provide novel insight into the underlying mechanisms of sarcopenia.