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

ADHIKARI, KAUSTUBH; REALES, G; SMITH, AJP; KONKA, E; PALMEN, J; QUINTO-SANCHÉZ, M; ACUÑA-ALONZO, V; JARAMILLO, CLAUDIA; ARIAS, WILLIAMS; FUENTES, MACARENA; PIZARRO, MARÍA ; BARQUERA LOZANO, R; MACÍN PERÉZ, G; GÓMEZ-VALDÉS, J; VILAMIL-RAMIREZ, H; HÜNEMEIER T; RAMALLO, V.; CERQUEIRA, CCS; HURTADO, M; VILLEGAS, V; GRANJA, V; GALLO, C; POLETTI, G; SCHÜLER-FACCINI L; SALZANO FM; BORTOLINI, MC; CANIZALES-QUINTEROS, S; ROTHHAMMER, F; BEDOYA, G; CALDERÓN, R; ROSIQUE, JAVIER; CHEESEMAN, M; BHUTTA, MF; HUMPHRIES, S; GONZALEZ-JOSÉ R; HEADON, D; BALDING, D; RUIZ LINARES A

NATURE COMMUNICATIONS

Macmillan Publishers Limited

Año: 2015 p. 1 - 10

2041-1723

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 2108 to 31014). 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.