Blood plasma proteome-wide association study implicates novel proteins in the pathogenesis of multiple cardiovascular diseases

BACKGROUND: Cardiovascular diseases (CVD) are the leading cause of global mortality, yet current treatments benefit only a subset of patients. To identify new potential treatment targets, we conducted the first proteome wide association study (PWAS) for 26 CVDs using plasma proteomics data from the largest cohort to date (53,022 individuals in the UK Biobank Pharma Proteomics Project (UKB-PPP)). METHODS AND RESULTS: ). We further conducted longitudinal analyses using plasma proteomics data and peripheral blood mononuclear cells single cell RNA-seq data. The results showed that 90.63% (29/32) of the detected proteins exhibited stable plasma expression, and 18 genes displayed stable expression in at least one cell type, particularly in CD14+ monocytes. We also utilized these proteins to construct disease diagnostic models, and notably, models for 14 out of 18 diseases achieved an area under the curve (AUC) exceeding 0.8, indicating promising diagnostic potential. CONCLUSIONS: 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.