A bi-directional Mendelian randomization study of the sarcopenia-related traits and Primary gonarthrosis

Abstract Background: Sarcopenia and primary gonarthrosis are common prevalent diseases in elderly people. Previous studies have reported a close association between the two, but causation was prone to confounding factors. A more robust research approach is urgently required to investigate the causal relationship between sarcopenia and primary gonarthrosis. Methods: The bi-directional two-sample Mendelian randomization (MR) analyses was carried out to explore causal inference between sarcopenia-related traits and primary gonarthrosis. The open GWAS database established by the MRC Integrated Epidemiology Unit (IEU) and FinnGen database provided the summary-level data used in this investigation. The GWAS summary data for appendicular lean mass (ALM, n=450,243), low hand grip strength(n=256,523), hand grip strength (left)(n=461,089), hand grip strength (right)(n=461,089) and usual walking pace (n=459,915) were used as sarcopenia-related traits. The GWAS summary data for knee osteoarthritis (KOA, n=403,124), primary gonarthrosis (n=285,550) and primary gonarthrosis, surgery (n=356,322) were used as phenotypes for primary gonarthrosis. The inverse-variance weighted (IVW) approach was used to obtain MR estimates, and various sensitivity analysis was also performed. Results: Increased hand grip strength (right) reduced the risk of gonarthrosis surgery (OR = 0.702; p = 0.0308). Furthermore, the risk of knee diseases and knee surgery was reduced by increasing walking pace. Correspondingly, gonarthrosis significantly reduces usual walking pace. Unexpectedly, our findings support a positive association between ALM and primary gonarthrosis. But it turns to less significant (p > 0.05) after conducting multivariable Mendelian randomization (MVMR) analyses combining Body mass index (BMI) and height. Conclusion: Sarcopenia-related traits (hand-grip strength and walking pace) may lead to the occurrence and progression of primary gonarthrosis. But there is insufficient evidence that gonarthrosis causes sarcopenia.