A genome-wide association study identifies multiple loci for variation in human ear morphology

Nat Commun. 2015 Jun 24;6:7500. doi: 10.1038/ncomms8500.


Here we report a genome-wide association study for non-pathological pinna morphology in over 5,000 Latin Americans. We find genome-wide significant association at seven genomic regions affecting: lobe size and attachment, folding of antihelix, helix rolling, ear protrusion and antitragus size (linear regression P values 2 × 10(-8) to 3 × 10(-14)). Four traits are associated with a functional variant in the Ectodysplasin A receptor (EDAR) gene, a key regulator of embryonic skin appendage development. We confirm expression of Edar in the developing mouse ear and that Edar-deficient mice have an abnormally shaped pinna. Two traits are associated with SNPs in a region overlapping the T-Box Protein 15 (TBX15) gene, a major determinant of mouse skeletal development. Strongest association in this region is observed for SNP rs17023457 located in an evolutionarily conserved binding site for the transcription factor Cartilage paired-class homeoprotein 1 (CART1), and we confirm that rs17023457 alters in vitro binding of CART1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • American Indian or Alaska Native / genetics
  • Animals
  • Cell Line, Tumor
  • Ear Auricle / anatomy & histology
  • Ear Auricle / embryology*
  • Edar Receptor / genetics*
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Homeodomain Proteins / metabolism
  • Humans
  • Latin America
  • Male
  • Mice
  • Morphogenesis / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide
  • T-Box Domain Proteins / genetics*
  • T-Box Domain Proteins / metabolism
  • White People / genetics
  • Young Adult


  • ALX1 protein, human
  • EDAR protein, human
  • Edar Receptor
  • Edar protein, mouse
  • Homeodomain Proteins
  • T-Box Domain Proteins
  • TBX15 protein, human