| Title: | Linear and non-linear proteome-wide association studies provide novel insight into venous thromboembolism |
| Journal: | Nature Communications |
| Published: | 15 Jul 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40664692/ |
| DOI: | https://doi.org/10.1038/s41467-025-61874-z |
| URL: | https://www.nature.com/articles/s41467-025-61874-z.pdf |
Publication 16996
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Abstract
Venous thromboembolism is a life-threatening vascular event with high prevalence and genetic determinants. PWAS has become a popular strategy to identify therapeutic targets of complex diseases. However, the current PWAS model only considers the linear relationship between protein and disease. Here, we propose a novel non-linear PWAS pipeline and identify 43 proteins exhibiting non-linear associations with venous thromboembolism in the UK Biobank, of which eight proteins cannot be captured by linear PWAS. We further conduct prospective cohort replication in the UK Biobank Pharma Proteomics Project, and replicate eight proteins with similar non-linear trends, including ULBP2, IL18BP, MAN1A2, CCL25, ICAM2, LGALS4, VSIG2 and ABO. Pathway enrichment analysis suggests that the identified non-linear proteins are involved in endothelium development, fluid shear stress and atherosclerosis pathways. In summary, we develop a novel non-linear PWAS analysis pipeline, and identify 43 non-linear proteins with venous thromboembolism, highlighting the importance of incorporating non-linear analysis in PWAS.</p>
11 Keywords
- Female
- Genome-Wide Association Study
- Humans
- Male
- Middle Aged
- Nonlinear Dynamics
- Prospective Studies
- Proteome
- Proteomics
- United Kingdom
- Venous Thromboembolism
10 Authors
- Yifan Kong
- Wangxia Tang
- Haonan Kang
- Yunlong Guan
- Si Li
- Xi Cao
- Zhonghe Shao
- Yi Jiang
- Chaolong Wang
- Xingjie Hao
1 Application
| Application ID | Title |
|---|---|
| 88159 | Fine-mapping, genetic correlation and genetic risk prediction for complex traits in different populations |
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