Abstract
Atherosclerotic cardiovascular disease (ASCVD) results in heart attack, stroke, and peripheral vascular disease and thus is one of the main causes of death in developed countries. Until the beginning of this century it has been widely assumed that ASCVD is a modern disease of affluence connected to an unhealthy lifestyle. Current studies, however, display growing evidence for the presence of atherosclerosis in ancient human remains. In addition, in modern medicine genetic predispositions gain an increasingly importance in the understanding of the development of ASCVD. However, genetic data about the prevalence of the disease associated single nucleotide polymorphisms (SNPs) in our ancestors is almost lacking.
Here, we present for the first time, a polygenic risk score (PRS) for ASVCD in human remains based on 87 SNPs in 56 genes that were associated to ASCVD in genome-wide association studies. We analysed ancient human genomes from various geographic origins and time periods, including mummies from South America, Australia, Egypt, and Europe. Next-generation sequencing methods, including a novel enrichment approach designed specifically to capture ASCVD associated SNPs, have been applied. Genetic results were compared to the physical occurrence or absence of atherosclerotic plaques visible on computed tomography scans of the analysed individual.
Our study provides more insights into the presence and possible changes of genetic risk factors in our ancestors. Comparing the PRS to the different lifestyles of the past could lead to a better understanding of the interaction between environmental and genetic influences on the development of ASCVD.