A bi-directional Mendelian randomization study of sarcopenia-related traits and renal function.

Abstract

The association between sarcopenia and renal function has been reported in observational studies; however, the directionality and potential causal nature of these associations remain uncertain. We assessed whether genetically predicted sarcopenia-related traits are associated with renal function and vice versa using bidirectional Mendelian randomization (MR). We conducted a bidirectional two-sample MR analysis using publicly available European-ancestry GWAS summary statistics for appendicular lean mass (ALM), hand-grip strength (left and right), and walking pace, and for renal function (cystatin C-based estimated glomerular filtration rate [eGFRcystatin C] and urinary albumin excretion [UAE]). Causal estimates were primarily obtained using inverse-variance weighted (IVW) models, complemented by sensitivity analyses (MR-Egger intercept, weighted median/mode, MR-PRESSO, Radial MR, and leave-one-out). In forward MR, genetically predicted walking pace was positively associated with eGFRcystatin C. Genetically predicted ALM and grip strength (right and left) were inversely associated with UAE. In reverse MR, genetically predicted UAE was inversely associated with ALM and right-hand grip strength. Estimates were broadly consistent across sensitivity analyses, and outlier-robust analyses (MR-PRESSO/Radial MR) yielded similar results. These findings provide genetic evidence consistent with bidirectional relationships between sarcopenia-related traits and renal function (particularly UAE), under standard MR assumptions. Given potential limitations (e.g., heterogeneity, pleiotropy, and possible sample overlap), the results should be interpreted cautiously and complemented by other lines of evidence.