Evaluating the causal effect of circulating proteome on the risk of osteoarthritis-related traits.

ABSTRACT

OBJECTIVES: This study aims to identify circulating proteins that are causally associated with osteoarthritis (OA)-related traits through Mendelian randomisation (MR)-based analytical framework. METHODS: Large-scale two-sample MR was employed to estimate the effects of thousands of plasma proteins on 12 OA-related traits. Additional analyses including Bayesian colocalisation, Steiger filtering analysis, assessment of protein-altering variants and mapping expression quantitative trait loci to protein quantitative trait loci were performed to investigate the reliability of the MR findings; protein-protein interaction, pathway enrichment analysis and evaluation of drug targets were conducted to deepen the understanding and identify potential therapeutic targets of OA. RESULTS: Dozens of circulating proteins were identified to have putatively causal effects on OA-related traits, and a majority of these proteins were either drug targets or considered druggable. CONCLUSIONS: Through MR analysis, we have identified numerous plasma proteins associated with OA-related traits, shedding light on protein-mediated mechanisms and offering promising therapeutic targets for OA.