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

ADHIKARI, K; REALES G; SMITH, JP; KONKA, E; PALMEN, J; QUINTO-SÁNCHEZ M; ACUÑA-ALONZO, V; JARAMILLO, C; ARIAS, W; FUENTES, M; PIZARRO, M; BARQUERA LOZANO, R; MACÍN PEREZ, G; GÓMEZ-VALDÉS J; VILLAMIL-RAMIREZ, H; HUNEMEIER, T; RAMALLO, R; SILVA DE CERQUEIRA, C; HURTADO M; VILLEGAS V; GRANJA V; GALLO C; POLETTI, G; SCHULER-FACCINI L; SALZANO, FM; BORTOLINI, MC; CANIZALEZ-QUINTERO S; ROTHHAMMER, F; BEDOYA G; CALDERÓN R; ROSIQUE, J; CHEESEMAN, M; BHUTTA MF; HUMPHRIES SE; GONZÁLEZ JOSÉ, ROLANDO; 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 inover 5,000 Latin Americans. We find genome-wide significant association at seven genomicregions affecting: lobe size and attachment, folding of antihelix, helix rolling, ear protrusionand antitragus size (linear regression P values 2X10-8 to 3X10-14). Four traits areassociated with a functional variant in the Ectodysplasin A receptor (EDAR) gene, a keyregulator of embryonic skin appendage development. We confirm expression of Edar in thedeveloping mouse ear and that Edar-deficient mice have an abnormally shaped pinna. Twotraits are associated with SNPs in a region overlapping the T-Box Protein 15 (TBX15) gene, amajor determinant of mouse skeletal development. Strongest association in this region isobserved for SNP rs17023457 located in an evolutionarily conserved binding site for thetranscription factor Cartilage paired-class homeoprotein 1 (CART1), and we confirm thatrs17023457 alters in vitro binding of CART1.