Exploring genetic association of chronic kidney disease with sarcopenia among European population: a bidirectional Mendelian randomization study.

BACKGROUND

This study aims to investigate the bidirectional causal relationship between chronic kidney disease (CKD) and sarcopenia using two-sample Mendelian randomization (MR) analysis.

METHODS

A bidirectional MR analysis was performed using genetic data for CKD from the MEGASTROKE consortium and sarcopenia traits from the UK Biobank. SNPs associated with CKD and sarcopenia were used as instrumental variables. MR analysis was conducted with inverse variance weighting (IVW), weighted median, and MR-Egger methods. Sensitivity analyses included Cochran's Q test, MR-Egger intercept, and the leave-one-out method. Enrichment analysis was performed using GO and KEGG pathways.

RESULTS

The results indicate a positive association between CKD and both left-hand grip strength (OR = 1.03, 95% CI 1.01-1.04, P < 0.001) and right-hand grip strength (OR = 1.03, 95% CI 1.02-1.04, P < 0.001) for both sides. In addition, appendicular lean mass (ALM) was found to be positively associated with an increased risk of CKD (OR = 1.35, 95% CI 1.19-1.53, P < 0.001). However, no significant causal relationships were observed between CKD and ALM or usual walking pace. Enrichment analysis identified several relevant biological processes and pathways, such as DNA transcription regulation, protein degradation, and immune response pathways, that may mediate the relationship between CKD and sarcopenia.

CONCLUSIONS

This study provides evidence for a bidirectional causal relationship between CKD and sarcopenia, with CKD contributing to decreased hand grip strength and ALM being associated with an increased risk of CKD.