Causal association between sarcopenia-related traits and osteoarthritis: A bidirectional 2-sample Mendelian randomization Study

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Accumulating evidence from observational studies indicated that sarcopenia and osteoarthritis (OA) may interact in pathomechanism. Therefore, the present 2-sample Mendelian randomization (MR) study aimed to reveal the bidirectional causal association between sarcopenia-related traits and OA. We extracted instrumental variables strongly associated with sarcopenia-related traits, namely low grip strength, appendicular lean mass, and usual walking pace from 3 large-scale genome-wide association studies involving 256,523, 450,243, and 459,915 individuals, respectively. Summary-level data for knee and hip OA were obtained from a genome-wide association studies meta-analysis conducted by the UK Biobank and arcOGEN, involving 455,221 individuals of European descent. The inverse-variance weighted (IVW) method was utilized as primary MR analysis, whereas the weighted median, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO) were performed as complementary methods to verify the robustness of findings. Our findings indicated genetically predicted usual walking pace was inversely associated with hip OA (IVW OR = 0.30, 95 CI = 0.17-0.53, P = 4.27 × 10-5) as well as knee OA (IVW OR = 0.20, 95 CI = 0.12-0.33, P = 1.07 × 10-9). In the reverse MR analyses, genetically predicted hip OA (IVW beta = -0.027, 95 CI = -0.038, -0.016, P = 6.83 × 10-7) demonstrated a negative causal effect on usual walking pace, while knee OA (IVW beta =0.002, 95 CI = -0.031 to 0.035, P = .898) did not show a significant effect. However, no evidence was found to suggest a causal effect of low grip strength and appendicular lean mass on hip or knee OA, and vice versa. Our study suggests a negative causal effect of usual walking pace, a sarcopenia-related traits, on knee and hip OA, with hip OA also negatively affecting walking pace. Further research is needed to explore the mechanisms linking sarcopenia-related traits and site-specific OA, aiming to identify common therapeutic targets.