A multi-ancestry GWAS meta-analysis of facial features and its application in predicting archaic human features

Abstract

Facial morphology, a complex trait influenced by genetics, holds great significance in evolutionary research. However, due to limited fossil evidence, the facial characteristics of Neanderthals and Denisovans have remained largely unknown. In this study, we conduct a large-scale multi-ethnic meta-analysis of the genome-wide association study (GWAS), including 9674 East Asians and 10,115 Europeans, quantitatively assessing 78 facial traits using 3D facial images. We identify 71 genomic loci associated with facial features, including 21 novel loci. We develop a facial polygenic score (FPS) that enables the prediction of facial features based on genetic information. Interestingly, the distribution of FPSs among populations from diverse continental groups exhibits relevant correlations with observed facial features. Furthermore, we apply the FPS to predict the facial traits of seven Neanderthals and one Denisovan using ancient DNA and align predictions with the fossil records. Our results suggest that Neanderthals and Denisovans likely share similar facial features, such as a wider but shorter nose and a wider endocanthion distance. The decreased mouth width is characterized specifically in Denisovans. The integration of genomic data and facial trait analysis provides valuable insights into the evolutionary history and adaptive changes in human facial morphology.