Predicting skeletal stature using ancient DNA

Abstract

Objectives: Ancient DNA provides an opportunity to separate the genetic and environmental bases of complex traits by allowing direct estimation of genetic values in ancient individuals. Here, we test whether genetic scores for height in ancient individuals are predictive of their actual height, as inferred from skeletal remains. We estimate the contributions of genetic and environmental variables to observed phenotypic variation as a first step towards quantifying individual sources of morphological variation. Materials and Methods: We collected stature estimates and femur lengths from West Eurasian skeletal remains with published genome-wide ancient DNA data (n=167, dating from 33,000-850 BP). We also recorded genetic sex, genetic ancestry, date and paleoclimate data for each individual, and δ13C and δ15N stable isotope values where available (n=67). Results: A polygenic score (PRS) for height predicts 6.8% of the variance in femur length in our data (n=117, SD=0.0068%, p<0.001), controlling for sex, ancestry, and date. This is consistent with the predictive power of height PRS in present-day populations and the low coverage of ancient samples. Comparatively, sex explains about 15% of the variance in femur length in our sample. Environmental effects also likely play a role in variation, independent of genetics, though with considerable uncertainty (longitude: R2=0.0317, SD=0.009, p=0.019). Discussion: Polygenic scores explain a small but significant proportion of the variance in height in ancient individuals, though not enough to make useful predictions of individual phenotypes. However, environmental variables also contribute to phenotypic outcomes and understanding their interaction with direct genetic predictions will provide a framework with which to model how plasticity and genetic changes ultimately combine to drive adaptation and evolution.

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

“…When used to compute polygenic scores for ancient populations, only a subset of GWAS variants can be used, which substantially reduces predictive accuracy. Cox et al (2021) estimate that the combined effect of low-coverage and pseudo-haploid genotypes reduced their predictive accuracy by approximately 75%, when compared to present-day data.…”

“…Traits that are preserved in the fossil record can provide a degree of partial benchmarking (Cox et al, 2019(Cox et al, , 2021; however, the genetic components of variation are often only partially explained by polygenic scores, and environmental components almost always play large roles in expressed trait variation, often dwarfing the contribution of polygenic scores. Furthermore, only a few-largely osteological-traits are well preserved over time, so these comparisons will always be limited in scope.…”

“…They concluded that the changes in inferred standing height were partially predicted by genetics; with both measures remaining relatively constant between the Mesolithic and Neolithic, and increasing between the Neolithic and Bronze Age. A follow-up study by Cox et al (2021) used polygenic scores for height to show that PRS predicts 6.8% of the observed variance in femur length in ancient skeletons, after controlling for other variables. This is approximately one quarter of the predictive accuracy of PRS in present-day populations; which the authors attribute to the low-coverage aDNA data used in their study.…”

“…However, the inference of standing height from skeletal remains is not without its own problems. Both Cox et al (2021) and Marciniak et al (2021) used the method developed by Ruff et al (2012) to estimate stature from skeletal remains. Nevertheless, their respective estimates of stature—based on femur length—varied between some of the individuals included in both studies.…”

“…This greatly limits our ability to compare the genetically predicted value of a trait to its expressed phenotype, raising the question: are predictions of most ancient phenotypes inherently unverifiable? For well-preserved traits, like standing height, there is considerable variability in estimates produced from different skeletal elements and between different studies ( Cox et al, 2021 ; Marciniak et al, 2021 ). For traits that do not preserve well in the archaeological record, the prospects of validation are much poorer.…”