The human face represents a combined set of highly heritable phenotypes, but knowledge on its genetic architecture remains limited, despite the relevance for various fields. A series of genome-wide association studies on 78 facial shape phenotypes quantified from 3-dimensional facial images of 10,115 Europeans identified 24 genetic loci reaching study-wide suggestive association (p < 5 × 10-8), among which 17 were previously unreported. A follow-up multi-ethnic study in additional 7917 individuals confirmed 10 loci including six unreported ones (padjusted < 2.1 × 10-3). A global map of derived polygenic face scores assembled facial features in major continental groups consistent with anthropological knowledge. Analyses of epigenomic datasets from cranial neural crest cells revealed abundant cis-regulatory activities at the face-associated genetic loci. Luciferase reporter assays in neural crest progenitor cells highlighted enhancer activities of several face-associated DNA variants. These results substantially advance our understanding of the genetic basis underlying human facial variation and provide candidates for future in-vivo functional studies.

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Keywords European, face, gene regulation, genetics, genome-wide association study, genomics, GWAS, human, images
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Journal eLife
Xiong, Z. (Ziyi), Dankova, G. (Gabriela), Howe, L.J. (Laurence J.), Lee, M.K. (Myoung Keun), Hysi, P.G. (Pirro G.), de Jong, M.A, … Kayser, M.H. (2019). Novel genetic loci affecting facial shape variation in humans. eLife, 8. doi:10.7554/eLife.49898