Genetic predispostion of ASCVD in ancient human remians

Background and aims Several computed tomographic studies have shown the presence of atherosclerosis in ancient human remains. However, despite its importance to understand the development of atherosclerotic cardiovascular disease (ASCVD), genetic data concerning the prevalence of the disease associated single nucleotide polymorphisms (SNPs) in our ancestors is scarce. Here we applied an enrichment capture sequencing approach to mummified human remains from different geographic regions and time periods for a better understanding of the role of genetics in the evolution of ASCVD. Methods 22 mummified individuals were analysed for their genetic predisposition of ASCVD. Next-generation sequencing methods were applied to ancient DNA (aDNA) samples, including a novel enrichment approach specifically designed to capture SNPs associated with ASCVD in genome-wide association studies of modern humans. Results Five out of 22 ancient individuals passed all filter steps for calculating a weighted polygenic risk score (PRS) based on 87 SNPs in 56 genes. PRSs were correlated to scores obtained from contemporary people from around the world and cover their complete range. The genetic results of the ancient individuals reflect their 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. Conclusion We could show that alleles associated to ASCVD have been already widespread within the last 5000 years. 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.