Abstract: The genetic background of premature coronary artery disease (PCAD) includes two categories: rare mutations of single gene and the accumulation of common mutations of multiple genes. The pathogenic genes of the former are mainly related to lipid metabolism, vascular endothelial integrity, endothelial function, and thrombosis, among which LDL-C metabolism-related genes play an important role; the genetic background of the latter is similar to the common polygenic complex diseases, it is mainly investigated by genomic analysis tools, such as genome association analysis, quantitative trait loci analysis, multi-gene risk model and so on. Furthermore, the development of high-dimensional omics technologies and gene regulation networks (GRNs) also provide novel insights and important technical support for the interpretation of the genetic background of polygenic PCAD.