Exploring the Association between Plasma Proteins and Frailty Based on Mendelian Randomization and Network Pharmacology

Background Frailty is an emerging global burden of disease, characterized as an age-related clinical syndrome. Recent studies have suggested a potential link between plasma protein levels and the onset of frailty. This study aims to analyze the potential causal relationship between plasma proteins and frailty using a Mendelian Randomization (MR) study design. Methods Associations between plasma proteins and frailty were assessed using inverse variance weighted (IVW), MR-Egger regression, weighted median, maximum-likelihood method, and MR-PRESSO test. Protein-protein interaction network construction and gene ontology functional enrichment analysis were conducted on MR-identified target proteins. Results After FDR correction, MR analysis identified five plasma proteins, including BIRC2 [OR = 0.978, 95%CI(0.967–0.990)] and PSME1 [OR = 0.936, 95%CI(0.909–0.965)], as protective factors against frailty, and 49 proteins, including APOB [OR = 1.053, 95%CI(1.037–1.069)] and CYP3A4 [OR = 1.098, 95%CI(1.068,1.128)], as risk factors. Network pharmacology suggested BIRC2, PSME1, APOE, and CTNNB1 as key intervention targets. Conclusion This study employed MR design integrated with network pharmacology analysis to investigate the association between circulating plasma proteins and frailty, identified 5 plasma proteins negatively associated with frailty risk and 49 plasma proteins positively associated with frailty.