Shared and distinct pathways and networks genetically linked to coronary artery disease between human and mouse.
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Kurt Z, Cheng J, Barrere-Cain R, McQuillen CN, Saleem Z, Hsu N, Jiang N, Pan C, Franzén O, Koplev S, Wang S, Björkegren J, Lusis AJ, Blencowe M, Yang X
Elife 12 (-) - [2023-12-07; online 2023-12-07]
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.
NGI Uppsala (SNP&SEQ Technology Platform) [Service]
National Genomics Infrastructure [Service]
PubMed 38060277
DOI 10.7554/eLife.88266
Crossref 10.7554/eLife.88266
pmc: PMC10703441
pii: 88266