Exploring the causal link between circulating cytokines and sarcopenia traits: A Mendelian randomization analysis

Abstract Background Previous observational studies have linked circulating cytokines to sarcopenia, but their causal relationship remains unclear. This study employed Mendelian Randomization (MR) to investigate the causal links between circulating cytokines and sarcopenia‐related traits using genetic data. Methods A two‐sample bidirectional MR analysis was conducted using data from individuals of European ancestry, utilizing genome‐wide association studies (GWAS) statistics. The study selected instrumental single nucleotide polymorphisms (SNPs) significantly associated with circulating cytokines and applied multiple MR methods, including inverse variance weighted (IVW), Weighted Median, MR‐Egger, Weighted Mode, Simple Mode, and MR‐PRESSO. The traits analyzed were appendicular lean mass (ALM) and grip strength. Heterogeneity, robustness, and consistency of results were assessed using Cochran's Q statistic, MR‐Egger regression, and “leave‐one‐out” sensitivity analyses. Results The IVM‐MR analysis showed a casual association between genetically predicted circulating levels of interleukin‐16 and both ALM and grip strength (ALM: OR = 0.990, 95% CI: 0.980–1.000, p = .049; grip strength: OR = 0.971, 95% CI: 0.948–0.995, p = .020). Additionally, interferon‐gamma‐induced protein 10 (IP‐10), interleukin‐1‐beta (IL‐1β), and hepatocyte growth factor (HGF) were correlated with ALM and vascular endothelial growth factor (VEGF), interleukin‐12 (IL‐12), and interleukin‐5 (IL‐5) with grip strength. Comparable results were confirmed via the MR‐Egger, Weighted Median, Weighted Mode, and Simple Mode methods. Sensitivity analysis showed no horizontal pleiotropy to bias the causal estimates. Conclusion The results suggest a significant causal effect of inflammatory cytokines on sarcopenia, offering new avenues for therapeutic target development. However, the study's focus on a European ancestry cohort limits its generalizability to other populations. Future research should aim to include diverse ethnic groups to validate and broaden these findings, thereby enhancing our understanding of sarcopenia's mechanisms in a global context.