Chinese Journal of Pharmacovigilance ›› 2025, Vol. 22 ›› Issue (3): 241-248.
DOI: 10.19803/j.1672-8629.20240899

• Orginal Article • Previous Articles     Next Articles

Identification of Druggable Targets for Intervertebral Disc Degeneration Based on Multi-Omics Data-Driven Mendelian Randomization and Prediction of Traditional Chinese Medicine Interventions

GUO Dongqi1,2, WANG Hao,BAI Xin1, BAI Jianqi1, SU Hongmei1, ZHANG Jingru1, GUO Xiaofei1, ZHAO Xiaoqi4, WANG Min5, WANG Yuan1#, ZHANG Ping1,*   

  1. 1Department of Pathology, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing 100102, China;
    2Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China;
    3Office of Academic Development, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing 100102, China;
    4Department of Ultrasound, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing 100102, China;
    5Office of Human Resources, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing 100102, China
  • Received:2024-11-25 Online:2025-03-15 Published:2025-03-17

Abstract: Objective To identify druggable targets for the treatment of intervertebral disc degeneration (IDD), evaluate their safety, and to predict the traditional Chinese medicines (TCMs) that can regulate these druggable targets for IDD. Methods Data on expression quantitative trait loci of druggable genes was retrieved from the eQTLGen Consortium as exposures, while data on IDD genome-wide association study was downloaded from the GWAS Catalog to serve as outcomes for Mendelian randomization analysis intended to identify potential IDD therapeutic targets. Enrichment analyses were conducted on druggable genes related to IDD. The data on protein quantitative trait loci of druggable genes related to IDD was retrieved from the FinnGen database to validate the efficacy of these genes. A phenome-wide association study (PheWAS) via the PheWAS Portal was conducted to assess drug safety. The BATMAN-TCM 2.0 and ETCM 2.0 platforms were used to mine TCM components and analyze medication patterns. Potential lead compounds were identified through molecular docking of targets and TCM components on the CB-Dock 2 platform. Results 35 TCMs, including Corydalis yanhusuo W. T. Wang., Morinda officinalis How., and Artemisia argyi Lévl. et Vant., were found to treat IDD by regulating three druggable targets-ZP3, RRM2B, and CCL4, through their 20 active components. Gene expression MR indicated that 248 druggable genes were causally related to IDD, and enrichment analyses showed that these genes were associated with cytokine activities and cellular senescence. Protein MR validated six of these genes as druggable targets for IDD. PheWAS revealed no significant adverse effects associated with the aforementioned druggable targets. Molecular docking results showed good binding activity between the TCM components and the druggable targets, with the best binding energy of -10.2 kcal·mol-1. Conclusion Such genes as ZP3, RRM2B, and CCL4 are potential therapeutic targets for IDD with good safety profiles. TCMs like Morinda officinalis How., Corydalis yanhusuo W. T. Wang., and Artemisia argyi Lévl. et Vant. can treat IDD through these druggable targets, and their active components, such as Xanthosine, are potential compounds for new drug development.

Key words: Intervertebral Disc Degeneration, Mendelian Randomization, Drug Targets, Phenome-Wide Association Study, Safety, Traditional Chinese Medicine Prediction

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