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

Abstract Background Although there is a strong correlation between serum iron status and sarcopenia, there is insufficient comprehensive evidence to establish a definitive causal relationship between the two factors. Hence, the aim of this study is to employ Mendelian randomization techniques to elucidate the association between serum iron status and sarcopenia. Methods we conducted a bi-directional Mendelian randomization (MR) analysis. The analysis involved utilizing the inverse variance weighted (IVW), MR-Egger, and weighted median methods. Additionally, sensitivity analyses were performed to ensure the reliability of the obtained causal association results. Furthermore, an integrated proxy for iron status, derived from a combination of single nucleotide polymorphisms (SNPs), was employed in the MVMR analysis. Results The UVMR analyses demonstrated a significant causal effect of ferritin on appendicular lean mass (β= -0.051, 95%CI: -0.072~-0.031, p = 7.325×10− 07). Sensitivity analyses did not reveal any heterogeneity, pleiotropic effects, or fluctuations in the results due to outlying SNPs for the four iron status variables related to sarcopenia traits. Furthermore, the MVMR analyses indicated that ferritin (β= -0.068, 95%CI: -0.12~-0.017, p = 9.658×10− 03) plays a predominant role in the associations between iron status and appendicular lean mass. Conclusion 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.