The craniofacial shape of modern humans embodies genomic signatures of evolution, diversity, and clinical conditions

Abstract

Human craniofacial morphology is a hallmark of our species diversity and evolutionary history, shaped by adaptation, introgression, and global dispersal. Cranial globularization and chin emergence are well-documented morphological transformations whose genetic basis remains poorly understood, whereas Neandertal introgression is primarily documented through genomic evidence. How these evolutionary phenomena relate to craniofacial variation in present-day humans remains largely unresolved. Here, we leverage 3D craniofacial data from over 50,000 UK Biobank participants and employ a multivariate, multiscale genome-wide association approach to define axes of variation aligned with inter-population allele frequency shifts, evolutionary processes, and clinical conditions. We identify continuous craniofacial trends within our cohort that mirror global patterns of genetic diversity, indicating that facial differences between human populations arise at the phenotypic axes already present within a single population. We further demonstrate that modern human-derived alleles underlie the origins of the human chin by reducing midfacial projection relative to other hominins and reveal the persistent effects of Neandertal introgression on craniofacial diversity today. We also model genetically informed endophenotypes for orofacial clefts, obstructive sleep apnoea, and myopia. These findings provide insights into our species evolutionary history and endophenotypes of clinical conditions and establish a framework for contextualizing craniofacial diversity into biologically meaningful axes of variation relevant to diverse scientific disciplines.