An integrative skeletal and paleogenomic analysis of stature variation suggests relatively reduced health for early European farmers

Human culture, biology, and health were shaped dramatically by the onset of agriculture ~12,000 years before present (BP). This shift is hypothesized to have resulted in increased individual fitness and population growth as evidenced by archaeological and population genomic data alongside a decline in physiological health as inferred from skeletal remains. Here, we consider osteological and ancient DNA data from the same prehistoric individuals to study human stature variation as a proxy for health across a transition to agriculture. Specifically, we compared 'predicted' genetic contributions to height from paleogenomic data and 'achieved' adult osteological height estimated from long bone measurements for 167 individuals across Europe spanning the Upper Paleolithic to Iron Age (~38,000-2,400 BP). We found that individuals from the Neolithic were shorter than expected (given their individual polygenic height scores) by an average of -3.82 cm relative to individuals from the Upper Paleolithic and Mesolithic (P=0.040) and -2.21 cm shorter relative to post-Neolithic individuals (P=0.068, with osteological vs. expected stature steadily increasing across the Copper (+1.95 cm relative to the Neolithic), Bronze (+2.70 cm), and Iron (+3.27 cm) Ages. These results were attenuated when we additionally accounted for genome-wide genetic ancestry variation, for example with Neolithic individuals -2.82 cm shorter than expected on average relative to pre-Neolithic individuals (P=0.120). We also incorporated observations of paleopathological indicators of non-specific stress that can persist from childhood to adulthood in skeletal remains into our model. Overall, our work highlights the potential of integrating disparate datasets to explore proxies of health in prehistory.

约12000年前农业起源（距今，Before Present，BP）极大地塑造了人类的文化、生物学特征与健康状态。学界假说，这一转型不仅通过考古学与群体基因组学（population genomic）数据证实提升了个体适应度与种群规模，同时也如骨骼遗骸所推断的那样，导致了生理健康水平的下降。本研究针对同一批史前个体的骨学与古代DNA（ancient DNA）数据展开分析，以人类身高变异作为健康代用指标，探究农业转型过程中的健康变化。具体而言，我们针对欧洲范围内从旧石器时代晚期（Upper Paleolithic）至铁器时代（Iron Age）、时间跨度约38000至2400 BP的167例个体，对比了基于古基因组学（paleogenomic）数据预测得到的身高遗传贡献值，与通过长骨测量估算得到的实际成人骨学身高。我们发现，相较于旧石器时代晚期与中石器时代（Mesolithic）个体，新石器时代（Neolithic）个体的实际身高较基于其个体多基因身高评分（polygenic height scores）的预期平均低3.82厘米（P=0.040）；相较于新石器时代之后的个体，则平均低2.21厘米（P=0.068）。同时，骨学身高与预期身高在铜器时代（Copper Age，较新石器时代高1.95厘米）、青铜时代（Bronze Age，高2.70厘米）与铁器时代（Iron Age，高3.27厘米）中呈稳步上升趋势。当我们进一步纳入全基因组遗传祖源变异进行分析时，上述结果有所减弱：例如相较于新石器时代之前的个体，新石器时代个体的预期身高偏差平均仅为-2.82厘米（P=0.120）。我们还将骨骼遗骸中可从童年持续至成年的非特异性应激古病理学（paleopathological）指标纳入模型分析。总体而言，本研究彰显了整合多源异构数据集以探究史前健康代用指标的潜力。