Causal associations of circulating C-reactive protein with sarcopenia-related traits: A 2-sample Mendelian randomization study

This study aimed to evaluate the causal effect of C-reactive protein (CRP) on sarcopenia-related traits (grip strength and appendicular lean mass) utilizing a 2-sample Mendelian randomization (MR) approach. Instrumental variables were sourced from publicly accessible genome-wide association study datasets. To verify the heterogeneity and pleiotropy of the identified instrumental variables, the leave-one-out sensitivity analysis, MR pleiotropy residual sum and outlier test, and Cochran Q test were employed, respectively. Subsequently, 4 distinct models including the inverse-variance weighted model, weighted median estimator model, weighted model-based method, and MR-Egger regression (MER) model, were utilized in this MR analysis. After excluding all outliers identified by the MR pleiotropy residual sum and outlier test, no evident directional pleiotropy was found (right-hand grip strength: MER intercept = -0.000367, standard error [SE] = 0.000219, P = .095; left-hand grip strength: MER intercept = -00029, SE = 0.00023, P = .196; appendicular lean mass: MER intercept = -0.000434, SE = 0.00038, P = .255). The inverse-variance weighted analysis suggested a significant causal effect of genetically determined CRP on appendicular lean mass (beta = -0.03613, 95% confidence intervals [CI] [-0.05117--0.02109], P = 2.50 * 10-6) and grip strength (right hand: beta = -0.01507, 95% CI [-0.02379--0.00636], P = 6.99 * 10-4; left hand: beta = -0.01389, 95% CI [-0.02287--0.00491], P = .002), respectively. The results of the MR analysis support that genetically determined CRP may be causally associated with an increased risk of sarcopenia.