Blood plasma proteome-wide association study implicates novel proteins in the pathogenesis of multiple cardiovascular diseases
Authors' conclusion
We identified 72 proteins that causally influence CVD risk, providing new mechanistic insights into CVD and may prove to be promising targets as CVD therapeutics.
Study context
- Population
- UK Biobank Pharma Proteomics Project plasma proteomics (53,022 individuals) integrated with genome-wide association study (GWAS) summary statistics for 26 cardiovascular diseases (CVDs) (16 cardiac, 5 venous, 5 cerebrovascular) in up to 1,308,460 individualsUK Biobank Pharma Proteomics Project (UKB-PPP)
- Participants
- 53,022 participants
- Outcome
- Protein–CVD associations
Methodological detailsFUSION framework, replication in two independent plasma proteomic datasets, longitudinal analyses, Replication cohorts of 7213 and 3301 participants
- FUSION framework
- Replication in two independent plasma proteomic datasets
- Longitudinal analyses
- Replication cohorts of 7213 and 3301 participants
Main finding
As reported in the abstract
Proteins associated with CVDs
- Proteins associated with CVDs
- 155
- Proteins with evidence of a causal association (Mendelian randomization)
- 72
- Validated of available proteins
- 26 out of 35
- Proteins not previously implicated in GWAS of CVDs
- 33 of the 72
- PROC associated with VTE
- P = 6.32 × 10-7
Observational data: associations, not effects.
Further findings
Longitudinal stability of expression
- Detected proteins with stable plasma expression
- 90.63% (29/32)
- Genes with stable expression in ≥1 cell type, particularly CD14+ monocytes
- 18
Diagnostic models
- Diseases with model AUC exceeding 0.8
- 14 out of 18
Original publication
Blood plasma proteome-wide association study implicates novel proteins in the pathogenesis of multiple cardiovascular diseases. Cardiovasc Diabetol. Published 1 August 2025. doi:10.
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