| Title: | Diagnosis, Prognosis, and Drug Target Discovery for Chronic Widespread Pain: A Large Proteogenomic Study |
| Journal: | Advanced Science |
| Published: | 30 Sep 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41025730/ |
| DOI: | https://doi.org/10.1002/advs.202507691 |
Publication 19367
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Abstract
Chronic widespread pain (CWP) remains challenging due to its heterogeneous causes and complex mechanisms. A total of 2920 plasma proteins are analyzed from 29,254 UK Biobank participants. A total of 256 proteins are identified as cross-sectionally correlated with CWP. A simple (top 10 proteins) and comprehensive (all significant proteins) proteomic-based score (ProtS) is created for CWP diagnosis, both outperforming and improving the existing clinical score (area under the curve, AUC: 0.801, 0.723, and 0.791 alone, and 0.856 and 0.880 in combination). In addition, the protein score predicted 13-years risk of pain-related traits over the body, including pain onset, progression, and intensity; Moreover, it has stronger associations with nociplastic pain and fibromyalgia compared to nociceptive and neuropathic pain, implying a unique protein signature of different pain mechanisms. Finally, among 434 candidate proteins prioritized in the observational analysis, 18 are corroborated with causal relevance by Mendelian randomization, and importantly, four (CA14, DPEP1, LGALS3, and TNF) showed potential as novel drug targets repurposed for treating CWP.</p>
17 Authors
- Li Chen
- Eoin Kelleher
- Ruogu Meng
- Duanke Liu
- Yuchen Guo
- Yunhe Wang
- Yaqing Gao
- Zhe Huang
- Zhu Liang
- Shuai Yuan
- Chao Zeng
- Jun Ma
- Yanhui Dong
- Anushka Irani
- Guanghua Lei
- Junqing Xie
- Daniel Prieto-Alhambra
1 Application
| Application ID | Title |
|---|---|
| 98358 | Real-world data linked to genetics and biomarkers to triangulate the evidence on the risk-benefit of medical products |
Enabling scientific discoveries that improve human health