Iron status and sarcopenia-related traits: a bi-directional Mendelian randomization study

Although serum iron status and sarcopenia are closely linked, the presence of comprehensive evidence to establish a causal relationship between them remains insufficient. The objective of this study is to employ Mendelian randomization techniques to clarify the association between serum iron status and sarcopenia. We conducted a bi-directional Mendelian randomization (MR) analysis to investigate the potential causal relationship between iron status and sarcopenia. MR analyses were performed using inverse variance weighted (IVW), MR-Egger, and weighted median methods. Additionally, sensitivity analyses were conducted to verify the reliability of the causal association results. Then, we harvested a combination of SNPs as an integrated proxy for iron status to perform a MVMR analysis based on IVW MVMR model. UVMR analyses based on IVW method identified causal effect of ferritin on appendicular lean mass (ALM, β = - 0.051, 95% CI - 0.072, - 0.031, p = 7.325 × 10^-07). Sensitivity analyses did not detect pleiotropic effects or result fluctuation by outlying SNPs in the effect estimates of four iron status on sarcopenia-related traits. After adjusting for PA, the analysis still revealed that each standard deviation higher genetically predicted ferritin was associated with lower ALM (β = - 0.054, 95% CI - 0.092, - 0.015, p = 0.006). Further, MVMR analyses determined a predominant role of ferritin (β = - 0.068, 95% CI - 0.12, - 0.017, p = 9.658 × 10^-03) in the associations of iron status with ALM. Our study revealed a causal association between serum iron status and sarcopenia, with ferritin playing a key role in this relationship. These findings contribute to our understanding of the complex interplay between iron metabolism and muscle health.