This month in The Journal

Abstract

Complications stemming from atherosclerosis, the hardening of arteries due to a buildup of fats and cholesterol, is the leading cause of death in the United States. Although large-scale genomics studies have identified hundreds of risk loci and nominated critical cell types, a clear picture of relevant gene signatures and cell states has yet to emerge. One complicating factor is the difficulty of obtaining sufficient human tissue samples, especially those from unaffected individuals. In this issue, Örd et al. combine data from a mouse model of atherosclerosis with available human data to define and characterize crucial disease-associated cell states. Notably, the authors’ use of a mouse model enabled the use of single-cell RNA-seq to study aortic tissue during atherosclerotic disease progression. Prioritized gene sets point toward cell-state-specific and interrelated biological pathways that contribute to atherosclerotic phenotypes. The authors leverage these gene sets to develop a so-called “hybrid” polygenic risk score (PRS) for coronary artery disease that factors in the contribution of relevant cell states, cell types, and biological pathways. This work highlights the level of insight that can be achieved through integrative, cross-species analyses and provides fresh hypotheses to further explore atherosclerosis onset and progression.