Integrative Transcriptomic and Epigenomic Profiling for Signature Identification in Coronary Artery Disease: A Pilot Study

Coronary Artery Disease (CAD), mainly due to the progressive development of atherosclerotic plaques, is one of the world's leading causes of mortality and morbidity. A significant percentage of initial events (around 30%) remain fatal to this day despite significant advances in the diagnosis and treatment of cardiovascular diseases (CVDs). Early detection and risk stratification are therefore essential. In this study, we adopted a multi-omics approach integrating transcriptomic (RNA-seq) and epigenomic (ATAC-seq) profiling of peripheral blood mononuclear cells (PBMCs) from a cohort of individuals undergoing clinically indicated cardiac computed tomography angiography (CCTA) to uncover potential novel molecular markers of CAD. We identified 39 genes consistently dysregulated across all CAD subtypes. ATAC-seq analysis revealed distinct chromatin accessibility patterns at CAD-associated loci, with a predominance of quiescent and transcriptionally active states. Validation in an independent cohort confirmed the expression patterns of key Differentially Expressed Genes (DEGs), such as <i>Claudin 18 (CLDN18)</i>, supporting the robustness of our findings. Consequently, the integration of multi-omics data allowed us to identify a core gene signature and regulatory patterns associated with disease severity, offering potential biomarkers for clinical risk stratification in patients with CAD.