Automatic landmarking identifies new loci associated with face morphology and implicates Neanderthal introgression in human nasal shape

A genome-wide association study and fully automatic landmarking approach on frontal 2D face photographs of >6000 Latin Americans identifies novel genomic regions influencing facial features and implicates Neanderthal introgression in nasal shape. We report a genome-wide association study of facial features in >6000 Latin Americans based on automatic landmarking of 2D portraits and testing for association with inter-landmark distances. We detected significant associations (P-value <5 x 10(-8)) at 42 genome regions, nine of which have been previously reported. In follow-up analyses, 26 of the 33 novel regions replicate in East Asians, Europeans, or Africans, and one mouse homologous region influences craniofacial morphology in mice. The novel region in 1q32.3 shows introgression from Neanderthals and we find that the introgressed tract increases nasal height (consistent with the differentiation between Neanderthals and modern humans). Novel regions include candidate genes and genome regulatory elements previously implicated in craniofacial development, and show preferential transcription in cranial neural crest cells. The automated approach used here should simplify the collection of large study samples from across the world, facilitating a cosmopolitan characterization of the genetics of facial features.

Automated summary

A genome-wide association study and automatic landmarking approach on 2D face photographs of over 6000 Latin Americans reveal novel genomic regions influencing facial features and suggest Neanderthal influence on nasal shape. The study detected significant associations at 42 genome regions, with 33 new regions replicating in East Asians, Europeans, or Africans. The findings provide insights into the genetics of facial features and suggest a simplified method for large-scale studies across populations.