The association between inflammatory cytokines and sarcopenia-related traits: a bi-directional Mendelian randomization study

Abstract

Sarcopenia is among the most common musculoskeletal illnesses, yet its underlying biochemical mechanisms remain incompletely understood. Identifying the relationship of inflammatory cytokines with sarcopenia components would help understand the etiology of sarcopenia. We performed a bi-directional Mendelian randomization study to explore the causal relationship between 41 inflammatory cytokines and sarcopenia-related traits. The study was performed in two stages using bidirectional dual-sample Mendelian randomization. We obtained aggregated statistical data on inflammatory factors, low grip strength, and ALM from genome-wide association studies. To explore the causal association between exposure and outcomes, we primarily utilized the inverse variance weighted strategy. Furthermore, we conducted sensitivity analyses through the use of Mendelian randomization (MR) Egger, weighted median and simple mode methods. To evaluate robustness of the results and to identify and adjust for horizontal pleiotropy, we performed the MR Pleiotropy RESidual Sum and Outlier test, the MR Egger intercept test, and a leave-one-out analysis. The results displayed a potential association between interleukin-10 (OR: 1.046, 95% CI: 1.002–1.093, p = 0.042) and vascular endothelial growth factor (OR: 1.024, 95% CI: 1.001–1.047, p = 0.038) and the risk of low hand-grip strength. Moreover, interferon gamma-induced protein 10 (OR: 1.010, 95% CI: 1.000–1.019, p = 0.042) and macrophage colony-stimulating factor (OR: 1.010, 95% CI: 1.003–1.017, p = 0.003) were significantly linked to a higher risk of ALM. We identified a causal relationship between multiple inflammatory factors and sarcopenia-related traits. Our study offers valuable insights into innovative methods for the sarcopenia prevention and treatment by regulating inflammatory factors.