Plasma proteomic profiles identify biomarkers predicting Crohn’s disease up to 16 years before onset
Reliable tools for early identification of Crohn's disease (CD) remain lacking. We analyzed 2736 plasma proteins in 39,634 UK Biobank (UKB) participants and identified 44 associated with incident CD. CD274, CHI3L1, REG1B, ITGAV, PRSS8, ITGA11, GDF15, DEFA1_DEFA1B, and IL6 ranked highest in protein importance ordering. A machine learning model based on these 9 proteins achieved high prediction for CD in a geographically distinct UKB testing cohort (n = 13,262, AUC 0.76), outperforming clinical risk models. It was externally validated in EPIC-Norfolk (n = 2944, AUC 0.73) and exhibited high discriminatory capacity for CD in the cross-sectional Southern China cohort (n = 74, AUC 0.79). In the UKB testing cohort, combining proteins with clinical data improved predictive performance (AUC 0.78) up to 16 years pre-diagnosis. In the same cohort, individuals at high risk stratified by the protein model were 4.23 times more likely to develop CD. Our findings highlight proteomics-based models as a promising approach to predict CD up to 16 years before diagnosis, offering opportunities for early screening and intervention.
Authors
- Dongling Luo (ORCID: https://orcid.org/0000-0003-3188-2248)
- Meijun Meng
- Chongyang Duan (ORCID: https://orcid.org/0000-0001-7973-0353)
- Yuying Ma
- Lingyi Li (ORCID: https://orcid.org/0000-0001-6221-7270)
- Long Yu (ORCID: https://orcid.org/0000-0002-6388-0688)
- Hao Chen (ORCID: https://orcid.org/0000-0003-4339-3441)
- Han Zhang (ORCID: https://orcid.org/0000-0003-2016-4179)
- Wentao Huang (ORCID: https://orcid.org/0000-0002-7872-8996)
- Weihong Sha (ORCID: https://orcid.org/0000-0003-4180-5211)
- Shiyi Yu (ORCID: https://orcid.org/0009-0008-0980-5303)
- Ruijie Zeng (ORCID: https://orcid.org/0000-0002-9803-0157)
- Jing Feng (ORCID: https://orcid.org/0000-0002-7425-2994)
- Chunling Chen (ORCID: https://orcid.org/0000-0001-8381-8710)
- Qinming Li
- Felix W. Leung
- Yanjun Wu (ORCID: https://orcid.org/0009-0007-3861-5712)
- Lijun Zhang (ORCID: https://orcid.org/0000-0003-4974-2745)
- Shuo Chen (ORCID: https://orcid.org/0000-0002-0678-7380)
Institutions
- University of California, Los Angeles (US)
- Chinese Academy of Sciences (CN)
- Shantou University (CN)
- Nanfang Hospital (CN)
- Shantou University Medical College (CN)
- VA Sepulveda Ambulatory Care Center (US)
- Guangdong Academy of Medical Sciences (CN)
- Shenzhen Institutes of Advanced Technology (CN)
- Guangdong Provincial People's Hospital (CN)
- Southern Medical University (CN)
- University of Hong Kong (HK)
- South China University of Technology (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-12
- DOI
- https://doi.org/10.1038/s41467-025-66483-4
- Citations
- 1
- Primary Topic
- Inflammatory Bowel Disease
- Type
- article
- Field-Weighted Citation Impact
- 1.82
Funders
- American Society for Gastrointestinal Endoscopy
- Cancer Research UK
- National Natural Science Foundation of China
- Southern Medical University
- Guangdong Provincial People's Hospital
- Medical Research Council
- Natural Science Foundation of Guangdong Province for Distinguished Young Scholars
- Basic and Applied Basic Research Foundation of Guangdong Province