Shared and distinct pathways and networks genetically linked to coronary artery disease between human and mouse

Zeyneb Kurt, Jenny Cheng, Caden N McQuillen, Zara Saleem, Neil Hsu, Nuoya Jiang, Rio Barrere-Cain, Calvin Pan, Oscar Franzen, Simon Koplev, Susanna Wang, Johan Bjorkegren, Aldons J Lusis, Montgomery Blencowe*, Xia Yang*

*Corresponding author for this work

Research output: Working paperPreprint

2 Citations (Scopus)
11 Downloads (Pure)

Abstract

Mouse models have been used extensively to study human coronary artery disease (CAD) and to test therapeutic targets. However, whether mouse and human share similar genetic factors and pathogenic mechanisms of CAD has not been thoroughly investigated in a data-driven manner. We conducted a cross-species comparison study to better understand CAD 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.

Original languageEnglish
Place of PublicationCambridge
PublishereLife Sciences Publications Ltd.
Pages1-36
Number of pages36
DOIs
Publication statusPublished - 10 Aug 2023

Publication series

NameComputational and Systems Biology
PublishereLife Sciences Publications Ltd.
No.RP88266
Volume12
ISSN (Electronic)2050-084X

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