A Mendelian randomization study investigating the causal role of inflammation Cytokines on Sarcopenia

Abstract Background: Sarcopenia is a disorder of the skeletal muscles characterized by a reduction in muscle mass, strength, and function. This investigation investigates the potential causal connection between inflammatory cytokines and sarcopenia. Methods: Using two genome-wide association studies (GWAS), we performed bidirectional Mendelian randomization (MR) analysis. The statistical analyses mainly included inverse variance-weighted (IVW), weighted median (WM), MR-Egger, Cochran's Q test, MR-Egger intercept analysis, and MR-PRESSO. Results: By the European Working Group on Sarcopenia in Older People (EWGSOP) criteria, we observed an inverse correlation between IL16 and sarcopenia (IL16, odds ratio [OR]: 0.971, 95% confidence interval [CI]: 0.948-0.995, P = 0.0199). In contrast, IL5 and MIP1b were positively associated with sarcopenia (IL5, OR: 1.063, 95% CI: 1.006-1.124, P = 0.0294; MIP1b, OR: 1.022, 95% CI: 1.001-1.043, P = 0.0375). Using the Foundation for the National Institutes of Health (FNIH) standard, we found an inverse association between IL16 and the risk of developing sarcopenia (IL16, OR: 0.954, 95% CI: 0.917-0.993, P = 0.0223). In contrast, MIP1b showed a positive association with the risk of sarcopenia (MIP1b, OR: 1.027, 95% CI: 1.000-1.055, P = 0.0491). We observed a weak negative correlation between IL16 and appendicular lean mass (ALM) regarding muscle mass analysis (IL16, OR: 0.990, 95% CI: 0.980-0.999, P = 0.0498). Reverse magnetic resonance analysis revealed no causal relationships between sarcopenia and IL16, IL5, or MIP1b. Conclusion: Our research reveals a negative correlation between IL16 and genetic susceptibility to sarcopenia, indicating that IL16 protects effect on sarcopenia. In contrast, IL5 and MIP1b are positively associated with the risk of sarcopenia, suggesting they may be detrimental to muscle health.