Association Between Autoimmune Diseases and Sarcopenia: A Two-Sample Mendelian Randomization Study

Qing Su,1 Chen Jin,2 Yi Yang,1 Jingxian Wang,1 Juejin Wang,1 Hao Zeng,1 Yaqing Chen,1 Junxi Zhou,1 Yi Wang1 1Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Yi Wang, Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Chashan High Education Zone, Wenzhou, Zhejiang, 325035, People’s Republic of China, Tel +86-577-8669-9358, Email wang.yi@wmu.edu.cnPurpose: Observational studies have reported that autoimmune diseases are closely related to sarcopenia, but the causalities of autoimmune diseases with sarcopenia have not been established. We conducted this Mendelian randomization (MR) study to reveal the causal associations of overall autoimmune disease and five common autoimmune diseases with sarcopenia-related traits.Methods: The publicly available summary-level data of autoimmune diseases and three sarcopenia-related traits were used for analysis. The causal effects of autoimmune diseases on sarcopenia-related traits were first identified in discovery samples using the inverse-variance-weighted method as the primary method, and the robustness of results was examined by additional sensitivity analyses. Replication MR analyses were then conducted using replication samples of five autoimmune diseases. Finally, the possibility of reverse causation was assessed by reverse MR analyses.Results: In both the discovery and replication samples, we identified potential causal effects of rheumatoid arthritis (RA) on appendicular lean mass (ALM) and low grip strength (OR = 0.979, 95% CI: 0.964– 0.995 for ALM; OR = 1.042, 95% CI: 1.013– 1.072 for low grip strength), but not on walking pace. We also found that inflammatory bowel disease (IBD) and type 1 diabetes (T1D) were only causally negatively associated with ALM in the discovery stage (OR = 0.986, 95% CI: 0.974– 0.999 for IBD; OR = 0.987, 95% CI: 0.975– 0.999 for T1D), whereas systemic lupus erythematosus, multiple sclerosis, and overall autoimmune disease were not associated with any of the three sarcopenia-related traits. Additionally, reverse MR analysis only found an association between walking pace and overall autoimmune disease, but this association did not remain in the weighted-median method.Conclusion: This study demonstrates that RA is causally associated with low grip strength and reduced ALM, and that IBD and T1D may be causally negatively related to ALM.Keywords: Mendelian randomization, autoimmune disease, sarcopenia, rheumatoid arthritis, grip strength, appendicular lean mass