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.
Data availability statement
Data are available in a public, open access repository.
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Handling editor Josef S Smolen
Twitter @YanZhang1716615, @valerietse_e
YZ, JX, SW and PC contributed equally.
Contributors GR and CD designed the research and directed the study. YZ wrote the manuscript and did the analyses. JX and SW did the analyses and developed the figures. PC developed the analytic skill and interpreted the results. WX, JZ, SL, ZW, HC, and ZZ reviewed the literature and extracted data from website. All authors commented on this paper and approved the final version. Responsibility for the overall content as guarantor: GR.
Funding This work has been fully supported by National Natural Science Foundation of China (81974342, 82003542 and 82002331), the Special Program of Chinese Postdoctoral Science Foundation (2022T150301) and Guangdong Basic and Applied Basic Research Foundation (2023A1515011518).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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