A genome-wide association scan implicates DCHS2 , RUNX2 , GLI3 , PAX1 and EDAR in human facial variation

We report a genome-wide associationscan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinalscale and found significant association(P values<5 × 10−8) at single-nucleotide polymorphisms ( SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nosebridge breadth (6p21) and nosewing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinalphenotypes and, also, a measure of nasionposition. Quantitative analyses confirmed the ordinal-based associations, identified SNPsin 2q12 associatedto chinprotrusion, and replicated the reported associationof nasionposition with SNPsin PAX3. Strongest associationin 2q12, 4q31, 6p21 and 7p13 was observed for SNPsin the EDAR, DCHS2, RUNX2and GLI3genes, respectively. Associated SNPsin 20p11 extend to PAX1. Consistent with the effect of EDAR on chinprotrusion, we documented alterations of mandible length in mice with modified Edar funtion.