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Osteoarthritis
Evaluating the causal effect of circulating proteome on the risk of osteoarthritis-related traits
  1. Yan Zhang1,
  2. Jingyu Xie2,
  3. Simin Wen3,
  4. Peihua Cao1,
  5. Wende Xiao4,
  6. Jianwei Zhu4,
  7. Shengfa Li1,
  8. Zhiqiang Wang1,
  9. Han Cen1,
  10. Zhaohua Zhu1,5,
  11. Changhai Ding1,3,
  12. Guangfeng Ruan1,3
  1. 1 Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
  2. 2 JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China
  3. 3 Clinical Research Centre, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
  4. 4 Department of orthopedics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
  5. 5 Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
  1. Correspondence to Prof. Changhai Ding, Clinical Research Centre, Zhujiang Hospital, Southern Medical University & Clinical Research Centre, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China; Changhai.Ding{at}utas.edu.au; Prof. Guangfeng Ruan, Clinical Research Centre, Guangzhou First People's Hospital, School of Medicine, South China University of Technology & Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; ruan1989.ok{at}163.com

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.

  • Epidemiology
  • Osteoarthritis
  • Polymorphism
  • Genetic
  • Cytokines

Data availability statement

Data are available in a public, open access repository.

http://dx.doi.org/10.1136/ard-2023-224459

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    Data availability statement

    Data are available in a public, open access repository.

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    Footnotes

    • 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.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.