Title
A genome-wide association study identifies multiple loci for variation in human ear morphology
Date Issued
24 June 2015
Access level
open access
Resource Type
journal article
Author(s)
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.
Granja V.
Schuler-Faccini L.
Salzano F.M.
Bortolini M.C.
Canizales-Quinteros S.
Rothhammer F.
Bedoya G.
Calderón R.
Rosique J.
Cheeseman M.
Bhutta M.F.
Humphries S.E.
Gonzalez-José R.
Headon D.
Balding D.
Ruiz-Linares A.
Publisher(s)
Nature Publishing Group
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<sup>-8</sup> to 3 × 10<sup>-14</sup>). 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.
Volume
6
Language
English
OCDE Knowledge area
Genética humana
Scopus EID
2-s2.0-84933039617
PubMed ID
Source
Nature Communications
ISSN of the container
20411723
Sponsor(s)
We thank the volunteers for their enthusiastic support. We also thank Alvaro Alvarado, Mónica Ballesteros Romero, Mari-Wyn Burley, Ricardo Cebrecos, Debajyoti Choudhury, Miguel Ángel Contreras Sieck, Francisco de Ávila Becerril, Joyce De la Piedra, María Teresa Del Solar, Paola Everardo Martínez, William Flores, Martha Granados Riveros, Wendy Hart, Ilich Jafet Moreno, Jodie Lampert, Mowmita Basak Mow, Paola León-Mimila, Javier Mendoza, Francisco Quispealaya, Diana Rogel Diaz, Ruth Rojas, Norman Russell, Vanessa Sarabia and Fabienne Tessiot for assistance with volunteer recruitment, sample processing and data entry. We are very grateful to the institutions that kindly provided facilities for the assessment of volunteers, including: Escuela Nacional de Antropología e Historia and Universidad Nacional Autónoma de México (Mexico); Pontificia Universidad Católica del Perú, Universidad de Lima and Universidad Nacional Mayor de San Marcos (Peru). This work was funded by grants from the Leverhulme Trust (F/07 134/DF to A.R.-L.), BBSRC (BB/I021213/1 to A.R.-L. and Institute Strategic Programme grant to The Roslin Institute), Universidad de Antioquia (GENMOL sostenibilidad 2015–2016 and MASO 2013–2014). S.E.H. holds a British Heart Foundation Chair and acknowledges funding from grant RG008/08 and is also supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. A.J.P.S. is funded by a BHF Fellowship (FS/13/6/29977).
Sources of information:
Directorio de Producción Científica
Scopus