Shared and distinct pathways and networks genetically linked to coronary artery disease between human and mouse
Year: 2023
Type: article
Abstract: Mouse models have been used extensively to study human coronary artery disease (CAD) or atherosclerosis and to test therapeutic targets. However, whether mouse and human share similar genetic factors and pathogenic mechanisms of atherosclerosis has not been thoroughly investigated in a data-driven manner. We conducted a cross-species comparison study to better understand atherosclerosis pathogenesis between species by leveraging multiomics data. Specifically, we compared genetically driven and thus CAD-causal gene networks and pathways, by using human GWAS of CAD from the CARDIoGRAMplusC4D consortium and mouse GWAS of atherosclerosis from the Hybrid Mouse Diversity Panel (HMDP) followed by integration with functional multiomics human (STARNET and GTEx) and mouse (HMDP) databases. We found that mouse and human shared >75% of CAD causal pathways. Based on network topology, we then predicted key regulatory genes for both the shared pathways and species-specific pathways, which were further validated through the use of single cell data and the latest CAD GWAS. In sum, our results should serve as a much-needed guidance for which human CAD-causal pathways can or cannot be further evaluated for novel CAD therapies using mouse models.
Source: eLife
DOI: 10.7554/elife.88266
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: Systems genetics approach to inflammatory mechanisms in atherosclerosis, Cross-species Comparison of Genetic Networks of Cardiometabolic Disorders, Delineating gene networks linking non-alcoholic fatty liver disease to CVD, An integrated systems approach to decipher cell-level gene-regulatory circuits necessary for developing precision medicine for cardiometabolic disorders and coronary artery disease, G3651446639, Defining the Roles of Smooth Muscle Cells and Other Extracellular Matrix Producing Cells in Late Stage Atherosclerotic Plaque Pathogenesis, G4610422777, Understanding the Molecular Mechanisms of Fibromuscular Dysplasia, G6888456212, G712881263, AtheroGEN, G7616092676, G7687471651, Integrated systems genetics applied to high-dimensional data from multiple tissues, the microbiome and portal vein to identify new diagnostic and therapy targets for cardiometabolic diseases in obese, Systems Genetics Dissection of Non-alcoholic Steatohepatitis, Systems Genetics of Vascular Smooth Muscle Phenotypes, Multimodal genetic regulatory architecture of coronary artery disease, Integrative genomic and functional genomic studies to connect variant to function for CAD GWAS loci, Functional genomics investigation of pleiotropic vascular disease loci
OpenAlex ID: W4385719713