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

Kaustubh Adhikari; Guillermo Reales; Andrew J.P. Smith; Esra Konka; Jutta Palmen; Mirsha Quinto-Sanchez; Victor Acuña-Alonzo; Claudia Jaramillo; William Arias; MacArena Fuentes; María Pizarro; Rodrigo Barquera Lozano; Gastón MacÍn Pérez; Jorge Gómez-Valdés; Hugo Villamil-Ramírez; Tábita Hunemeier; Virginia Ramallo; Caio C. Silva De Cerqueira; Malena Hurtado; Valeria Villegas; Vanessa Granja; Carla Gallo; Giovanni Poletti; Lavinia Schuler-Faccini; Francisco M. Salzano; Maria Cátira Bortolini; Samuel Canizales-Quinteros; Francisco Rothhammer; Gabriel Bedoya; Rosario Calderón; Javier Rosique; Michael Cheeseman; Mahmood F. Bhutta; Steve E. Humphries; Rolando Gonzalez-José; Denis Headon; David Balding; Andrés Ruiz-Linares

doi:10.1038/ncomms8500

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

Kaustubh Adhikari
, Guillermo Reales
, Andrew J.P. Smith
, Esra Konka
, Jutta Palmen
, Mirsha Quinto-Sanchez
, Victor Acuña-Alonzo
, Claudia Jaramillo
, William Arias
, MacArena Fuentes
, María Pizarro
, Rodrigo Barquera Lozano
, Gastón MacÍn Pérez
, Jorge Gómez-Valdés
, Hugo Villamil-Ramírez
, Tábita Hunemeier
, Virginia Ramallo
, Caio C. Silva De Cerqueira
, Malena Hurtado
, Valeria Villegas

Vanessa Granja, Carla Gallo, Giovanni Poletti, Lavinia Schuler-Faccini, Francisco M. Salzano, Maria Cátira Bortolini, Samuel Canizales-Quinteros, Francisco Rothhammer, Gabriel Bedoya, Rosario Calderón, Javier Rosique, Michael Cheeseman, Mahmood F. Bhutta, Steve E. Humphries, Rolando Gonzalez-José, Denis Headon, David Balding, Andrés Ruiz-Linares

University College London
Consejo Nacional de Investigaciones Científicas y Técnicas
National Institute of Anthropology and History
Universidad de Antioquia
Universidad de Tarapacá
Instituto Nacional de Medicina Genomica
Universidad Nacional Autónoma de México
Universidade Federal do Rio Grande do Sul
Universidad Peruana Cayetano Heredia
Complutense University
University of Edinburgh
Royal National Throat Nose and Ear Hospital
University of Melbourne

Research output: Contribution to journal › Article › peer-review

76 Scopus citations

Abstract

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.

Original language	English
Article number	7500
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8500
State	Published - 24 Jun 2015

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Adhikari, K., Reales, G., Smith, A. J. P., Konka, E., Palmen, J., Quinto-Sanchez, M., Acuña-Alonzo, V., Jaramillo, C., Arias, W., Fuentes, M., Pizarro, M., Barquera Lozano, R., MacÍn Pérez, G., Gómez-Valdés, J., Villamil-Ramírez, H., Hunemeier, T., Ramallo, V., Silva De Cerqueira, C. C., Hurtado, M., ... Ruiz-Linares, A. (2015). A genome-wide association study identifies multiple loci for variation in human ear morphology. Nature Communications, 6, Article 7500. https://doi.org/10.1038/ncomms8500

@article{bffddea1bf5f4c71961eb1ee7f83af60,

title = "A genome-wide association study identifies multiple loci for variation in human ear morphology",

abstract = "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.",

author = "Kaustubh Adhikari and Guillermo Reales and Smith, \{Andrew J.P.\} and Esra Konka and Jutta Palmen and Mirsha Quinto-Sanchez and Victor Acu{\~n}a-Alonzo and Claudia Jaramillo and William Arias and MacArena Fuentes and Mar{\'i}a Pizarro and \{Barquera Lozano\}, Rodrigo and \{Mac{\'I}n P{\'e}rez\}, Gast{\'o}n and Jorge G{\'o}mez-Vald{\'e}s and Hugo Villamil-Ram{\'i}rez and T{\'a}bita Hunemeier and Virginia Ramallo and \{Silva De Cerqueira\}, \{Caio C.\} and Malena Hurtado and Valeria Villegas and Vanessa Granja and Carla Gallo and Giovanni Poletti and Lavinia Schuler-Faccini and Salzano, \{Francisco M.\} and Bortolini, \{Maria C{\'a}tira\} and Samuel Canizales-Quinteros and Francisco Rothhammer and Gabriel Bedoya and Rosario Calder{\'o}n and Javier Rosique and Michael Cheeseman and Bhutta, \{Mahmood F.\} and Humphries, \{Steve E.\} and Rolando Gonzalez-Jos{\'e} and Denis Headon and David Balding and Andr{\'e}s Ruiz-Linares",

year = "2015",

month = jun,

day = "24",

doi = "10.1038/ncomms8500",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

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Adhikari, K, Reales, G, Smith, AJP, Konka, E, Palmen, J, Quinto-Sanchez, M, Acuña-Alonzo, V, Jaramillo, C, Arias, W, Fuentes, M, Pizarro, M, Barquera Lozano, R, MacÍn Pérez, G, Gómez-Valdés, J, Villamil-Ramírez, H, Hunemeier, T, Ramallo, V, Silva De Cerqueira, CC, Hurtado, M, Villegas, V, Granja, V, Gallo, C, Poletti, G, Schuler-Faccini, L, Salzano, FM, Bortolini, MC, Canizales-Quinteros, S, Rothhammer, F, Bedoya, G, Calderón, R, Rosique, J, Cheeseman, M, Bhutta, MF, Humphries, SE, Gonzalez-José, R, Headon, D, Balding, D & Ruiz-Linares, A 2015, 'A genome-wide association study identifies multiple loci for variation in human ear morphology', Nature Communications, vol. 6, 7500. https://doi.org/10.1038/ncomms8500

TY - JOUR

T1 - A genome-wide association study identifies multiple loci for variation in human ear morphology

AU - Adhikari, Kaustubh

AU - Reales, Guillermo

AU - Smith, Andrew J.P.

AU - Konka, Esra

AU - Palmen, Jutta

AU - Quinto-Sanchez, Mirsha

AU - Acuña-Alonzo, Victor

AU - Jaramillo, Claudia

AU - Arias, William

AU - Fuentes, MacArena

AU - Pizarro, María

AU - Barquera Lozano, Rodrigo

AU - MacÍn Pérez, Gastón

AU - Gómez-Valdés, Jorge

AU - Villamil-Ramírez, Hugo

AU - Hunemeier, Tábita

AU - Ramallo, Virginia

AU - Silva De Cerqueira, Caio C.

AU - Hurtado, Malena

AU - Villegas, Valeria

AU - Granja, Vanessa

AU - Gallo, Carla

AU - Poletti, Giovanni

AU - Schuler-Faccini, Lavinia

AU - Salzano, Francisco M.

AU - Bortolini, Maria Cátira

AU - Canizales-Quinteros, Samuel

AU - Rothhammer, Francisco

AU - Bedoya, Gabriel

AU - Calderón, Rosario

AU - Rosique, Javier

AU - Cheeseman, Michael

AU - Bhutta, Mahmood F.

AU - Humphries, Steve E.

AU - Gonzalez-José, Rolando

AU - Headon, Denis

AU - Balding, David

AU - Ruiz-Linares, Andrés

PY - 2015/6/24

Y1 - 2015/6/24

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84933039617

U2 - 10.1038/ncomms8500

DO - 10.1038/ncomms8500

M3 - Article

C2 - 26105758

AN - SCOPUS:84933039617

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 7500

ER -

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

Abstract

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