journal article·2025-12Open access

Diagnosis, Prognosis, and Drug Target Discovery for Chronic Widespread Pain: A Large Proteogenomic Study

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

Advanced Science· Volume 12· Issue 47

Abstract

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.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Fibromyalgia and Chronic Fatigue Syndrome Research · Pain Mechanisms and Treatments · Pain Management and Placebo Effect

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Centre for Statistics in Medicine and NIHR Biomedical Research Centre Oxford NDORMS University of Oxford Oxford OX3 7LD UK

Institute of Child and Adolescent Health School of Public Health Peking University Beijing 100191 China

Nuffield Department of Clinical Neurosciences University of Oxford Oxford OX3 9DU UK

National Institute of Health Data Science Peking University Beijing 100191 China

Beijing Institute of Ophthalmology Beijing Tongren Eye Center Beijing Key Laboratory of Ophthalmology and Visual Sciences Beijing Tongren Hospital, Capital Medical University Beijing 100730 China

Nuffield Department of Population Health University of Oxford Oxford OX3 7LF UK

Nuffield Department of Medicine Target Discovery Institute Center for Medicines Discovery University of Oxford Oxford OX3 7FZ UK

Department of Surgery Perelman School of Medicine at the University of Pennsylvania PA 19104 USA

Institute of Environmental Medicine Karolinska Institutet Stockholm 171 77 Sweden

Department of Orthopaedics Xiangya Hospital, Central South University Changsha 410013 China

Division of Rheumatology Mayo Clinic Florida Florida 32224 USA

The Queen's College University of Oxford Oxford OX1 4AW UK

Department of Medical Informatics Erasmus University Medical Center Rotterdam 3015 GD The Netherlands

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