Quantitative Human Paleogenetics: What can Ancient DNA Tell us About Complex Trait Evolution?

Abstract

Genetic association data from national biobanks and large-scale association studies have provided new prospects for understanding the genetic evolution of complex traits and diseases in humans. In turn, genomes from ancient human archaeological remains are now easier than ever to obtain, and provide a direct window into changes in frequencies of trait-associated alleles in the past. This has generated a new wave of studies aiming to analyse the genetic component of traits in historic and prehistoric times using ancient DNA, and to determine whether any such traits were subject to natural selection. In humans, however, issues about the portability and robustness of complex trait inference across different populations are particularly concerning when predictions are extended to individuals that died thousands of years ago, and for which little, if any, phenotypic validation is possible. In this review, we discuss the advantages of incorporating ancient genomes into studies of trait-associated variants, the need for models that can better accommodate ancient genomes into quantitative genetic frameworks, and the existing limits to inferences about complex trait evolution, particularly with respect to past populations.

Population differentiation of polygenic score predictions under stabilizing selection

“…With the rise of ancient DNA sequencing, GWAS from contemporary populations have also been used to construct polygenic scores for ancient individuals (reviewed in Irving-Pease et al ., 2021). These scores have been used to provide a window into the phenotypic diversity of past populations (Mathieson et al ., 2015; Berens et al ., 2017; Martiniano et al ., 2017) and to disentangle genetic and environmental contributors to temporal phenotypic variation (e.g.…”

“…We begin with the simplified case in which all causal loci that are polymorphic in population A have been identified, such that polygenic scores equal the additive genetic values in population A. As polygenic scores from ancient DNA are being used to investigate the phenotypic diversity of ancient human populations (Irving-Pease et al ., 2021), we first consider the prediction accuracy in a population ancestral to population A of a polygenic score constructed using variants found in population A. The reduction in polygenic score prediction accuracy for this ancestral population is approximately the reduction in variance contributed by that ancestral population to the present (Figure 2B,C; Figure S4; see Appendix A.3.2 for an explanation).…”

Population differentiation of polygenic score predictions under stabilizing selection

“…Thus, we caution that a better understanding of the portability of polygenic scores across populations also requires a stronger understanding of the causes of variation in prediction accuracy within populations. With the rise of ancient DNA sequencing, GWAS from contemporary populations have also been used to construct polygenic scores for ancient individuals (reviewed in [94]). These scores have been used to provide a window into the phenotypic diversity of past populations [106][107][108] and to disentangle genetic and environmental contributors to temporal phenotypic variation (e.g.…”

“…With the rise of ancient DNA sequencing, GWAS from contemporary populations have also been used to construct polygenic scores for ancient individuals (reviewed in [ 94 ]). These scores have been used to provide a window into the phenotypic diversity of past populations [ 106 – 108 ] and to disentangle genetic and environmental contributors to temporal phenotypic variation (e.g.…”

“…We begin with the simplified case in which all causal loci that are polymorphic in population A have been identified, such that polygenic scores equal the additive genetic values in population A. As polygenic scores from ancient DNA are being used to investigate the phenotypic diversity of ancient human populations [ 94 ], we first consider the prediction accuracy in a population ancestral to population A of a polygenic score constructed using variants found in population A. The reduction in polygenic score prediction accuracy for this ancestral population is approximately the reduction in variance contributed by that ancestral population to the present ( figure 2 b , c ; electronic supplementary material, figure S4; see appendix A, §c(ii) for an explanation).…”