Linking coronary artery disease to neurodegenerative diseases through systems genetics

Coronary artery disease (CAD) is still a leading cause of death worldwide despite the extensive research and the considerable progresses made through the years. As other cardiovascular diseases, CAD is the result of the complex interaction between genetic variants and environmental factors. Currently identified genetic loci associated to CAD revealed the contribution of multiple molecular pathways to its pathogenesis, suggesting the need for a systemic approach to understand the role of genetic determinants. In this study we wanted to investigate how GWAS variants associated to CAD interact with each other and with nearby genes in the context of the coronary artery molecular interactome. GWAS variants associated to CAD were selected from GWAS Catalog, then, a tissue-specific interactome was constructed integrating protein-protein interactions (PPI) from multiple public repositories and computationally inferred co-expression relationships. To focus on the part of the network most relevant for CAD, we selected the interactions connecting the genes carrying a variant associated to the disease. A functional enrichment analysis conducted on the subnetwork revealed that genes carrying ge