Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology

Numerous lines of evidence point to a genetic basis for facial morphology in humans, yet little is known about how specific genetic variants relate to the phenotypic expression of many common facial features. The authors conducted genome-wide association meta-analyses of 20 quantitative facial measurements derived from the 3D surface images of 3,118 healthy individuals of European ancestry belonging to two US cohorts. Analyses were performed on just under one million genotyped SNPs imputed to the 1,000 Genomes reference panel (Phase 3). The researchers observed genome-wide significant associations for cranial base width, intercanthal width, nasal width, nasal length, and upper facial depth. Several genes in the associated regions are known to play roles in craniofacial development or in syndromes affecting the face: MAFB, PAX9, MIPOL1, ALX3, HDAC8, and PAX1. Also tested were genotype-phenotype associations reported in two previous genome-wide studies and found evidence of replication for nasal ala length and SNPs in CACNA2D3 and PRDM16. These results provide further evidence that common variants in regions harboring genes of known craniofacial function contribute to normal variation in human facial features. Improved understanding of the genes associated with facial morphology in healthy individuals can provide insights into the pathways and mechanisms controlling normal and abnormal facial morphogenesis.