Causal association between sarcopenia and iron deficiency anemia: A two-sample Mendelian randomization study

To investigate potential causal links between sarcopenia and iron deficiency anemia (IDA), we conducted a two-sample Mendelian randomization (MR) study using genome-wide association study data. Instrumental variables were selected based on genome-wide significance ( P < 5 × 10 − ⁸), linkage disequilibrium pruning ( r 2 < 0.001), minor allele frequency > 0.01, and F -statistics > 10. Analysis used inverse-variance weighted method, with MR-Egger, weighted median, and weighted mode for robustness. Sensitivity analyses included Mendelian randomization pleiotropy residual sum and outlier, MR-Egger regression, Cochran Q , and leave-one-out analyses. Genetically predicted faster usual walking pace was associated with a reduced risk of both IDA secondary to chronic blood loss (OR = 0.375, P = .006) and IDA (OR = 0.534, P < .001). Genetically predicted higher right hand grip strength was associated with a reduced risk of IDA secondary to chronic blood loss (OR = 0.735, P = .04). However, no significant associations were observed for 5 other genetically predicted physical activity traits. In reverse MR analyses, IDA secondary to chronic blood loss was associated with reduced right hand grip strength (OR = 0.735, P = .04), while IDA was associated with a slower usual walking pace (OR = 0.973, P = .01), indicating a potential bidirectional relationship. Sensitivity analyses supported these findings. Lower muscle function is causally associated with increased IDA risk, while IDA may contribute to reduced muscle strength, suggesting a bidirectional relationship. Further research is needed to understand mechanisms and develop preventive strategies.