Unraveling Novel Therapeutic Targets for Coronary Artery Disease Via Gene Signatures of Plasma Proteome: a Mendelian Randomization Study

Abstract Background: Coronary Artery Disease (CAD) is a common disease with a significant healthcare burden across the globe. Efforts were made to identify therapeutic targets or prophylaxis for high-risk individuals. Method: Here, we used a plasma-proteomewide Mendelian Randomization approach to estimate the causal effect of plasma proteins on the development of CAD by using the pQTL of the proteins as the exposure, and two large-scale GWAS of CAD as the outcome. Results: We identified LPA, PCSK9, PLA2G7, C1S, C1R, ENO2, SNAP25, A1BG, and CA11 as risk proteins casually associated with the onset of CAD. C1S/R and ENO2 were prioritized as the first-tier targets. We further applied pathway enrichment analysis and RNA-seq data to show that aberrant activation of the complement system and glycolysis are casually associated with increased risk for CAD. Conclusion: In short, our study revealed novel therapeutic targets for the treatment of CAD, inviting further investigation into these targets and related pathways.