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

Nat Commun. 2016 May 19:7:11616. doi: 10.1038/ncomms11616.

Abstract

We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale 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), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar funtion.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anatomic Variation
  • Animals
  • Cadherin Related Proteins / genetics*
  • Core Binding Factor Alpha 1 Subunit / genetics*
  • Edar Receptor / genetics*
  • Face / anatomy & histology*
  • Genome-Wide Association Study
  • Humans
  • Latin America
  • Maxillofacial Development / genetics
  • Mice
  • Nerve Tissue Proteins / genetics*
  • Paired Box Transcription Factors / genetics*
  • Polymorphism, Single Nucleotide
  • Young Adult
  • Zinc Finger Protein Gli3 / genetics*

Substances

  • Cadherin Related Proteins
  • Core Binding Factor Alpha 1 Subunit
  • DCHS2 protein, human
  • EDAR protein, human
  • Edar Receptor
  • Edar protein, mouse
  • GLI3 protein, human
  • Nerve Tissue Proteins
  • Paired Box Transcription Factors
  • RUNX2 protein, human
  • Zinc Finger Protein Gli3
  • PAX1 transcription factor