Tissue-specific Network Analysis of Genetic Variants Associated with Coronary Artery Disease

Abstract

Coronary artery disease (CAD) is a leading cause of death worldwide. Recent genome-wide association studies have identified more than one hundred susceptibility loci associated with CAD. However, the underlying mechanism of these genetic loci to CAD susceptibility is still largely unknown. We performed a tissue-specific network analysis of CAD using the summary statistics from one of the largest genome-wide association studies. Variant-level associations were summarized into gene-level associations, and a CAD-related interaction network was built using experimentally validated gene interactions and gene coexpression in coronary artery. The network contained 102 genes, of which 53 were significantly associated with CAD. Pathway enrichment analysis revealed that many genes in the network were involved in the regulation of peripheral arteries. In summary, we performed a tissue-specific network analysis and found abnormalities in the peripheral arteries might be an important pathway underlying the pathogenesis of CAD. Future functional characterization might further validate our findings and identify potential therapeutic targets for CAD.