Exploring Causal Effects of Sarcopenia on Chronic Obstructive Pulmonary Disease and Hospitalization Risk: A Bi-Directional Mendelian Randomization Study

Aims/Background: As the global population ages, age-related chronic obstructive pulmonary disease (COPD) and sarcopenia present significant clinical and economic concerns. Emerging evidence suggests that these conditions are interrelated; however, potential confounding factors may impact observational investigations. Therefore, this study employed a bi-directional Mendelian randomization analysis to systematically investigate the causal relationship—rather than merely conducting a correlation analysis, between sarcopenia-related traits and COPD and hospitalization risk. Methods: Univariate, two-sample, and bi-directional Mendelian randomization (MR) analyses were performed using data from genome-wide association studies. The data on Sarcopenia features, including appendicular lean mass (ALM), hand grip strength (HGS), usual walking pace (UWP), and moderate-to-vigorous physical activity (MVPA) were acquired from the UK Biobank. However, data on COPD and hospitalization risk were sourced from the FinnGen consortium. Inverse-variance weighted (IVW) MR and sensitivity analyses were performed to evaluate causal relationships. Additionally, the observed findings were validated using an independent COPD dataset sourced from the UK Biobank. Results: The forward MR analysis using IVW revealed a significant negative causality between ALM, HGS, UWP, MVPA, and COPD (all p < 0.05, all pFDR < 0.05) (False Discovery Rate, FDR), as well as with COPD-related hospitalization (all p < 0.05, all pFDR < 0.05). These findings were corroborated by validation analyses. Furthermore, reverse MR assessment demonstrated that COPD alleviates UWP (p = 0.001, pFDR = 0.015); however, validation analysis did not confirm this result. Moreover, additional MR analyses yielded similar trends in causal relationships as evidenced by robust sensitivity tests. Conclusion: Our study supported a unidirectional, negative causality between sarcopenia-related traits and COPD and hospitalization risk. This provides possible evidence that sarcopenia increases the risk of COPD and hospitalization at the genetic level. Our findings suggest that improving sarcopenia may serve as a promising strategy for minimizing the incidence of COPD and hospitalization risk, thereby reducing the health burden on these patients.