Abstract
Atherosclerotic cardiovascular disease (ASCVD) results in heart attack, stroke, and peripheral vascular disease and is one of the main causes of death worldwide. Until recently, ASCVD was generally considered to be a modern disease and connected to an unhealthy lifestyle. However, recent studies show growing evidence for the presence of atherosclerosis in ancient human remains. In addition, genetic predisposition is becoming increasingly important in understanding the development of ASCVD. Nevertheless, genetic data concerning the prevalence of the disease associated single nucleotide polymorphisms (SNPs) in our ancestors is scarce.
Here, we present a weighted polygenic risk score (PRS) for ASVCD in human remains based on 87 SNPs in 56 genes that were associated with ASCVD in genome-wide association studies. We analysed ancient human genomes (N=22) of various geographic origins and time periods, including mummies from South America, Australia, Egypt, and Europe. Next-generation sequencing methods were applied, including a novel enrichment approach specifically designed to capture SNPs associated with ASCVD. A correlation of the calculated PRSs to scores obtained from contemporary people shows that the ancient individuals passing all filter steps, cover the complete range of PRSs acquired from modern individuals. Furthermore, their genetic results reflect the phenotypic results, as the only two mummies showing calcified atherosclerotic arterial plaques on computed tomography scans are the ones also exhibiting the highest calculated PRSs.
Our study provides further insights into the presence and possible changes of genetic risk factors in our ancestors. Comparing the PRS to the different lifestyles in the past has the potential to lead to a better understanding of the interaction between environmental and genetic influences on the development of ASCVD. In future studies, this could also help to understand the evolution of antagonistic pleiotropy.