title: A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation.
abstract: We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values<5 × 10(-8)) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar funtion.
authors.affiliation: Department of Genetics, Evolution and Environment, UCL Genetics Institute, University College London, London WC1E 6BT, UK.
authors.forename: Kaustubh
authors.initials: K
authors.lastname: Adhikari
authors.affiliation: Department of Genetics, Evolution and Environment, UCL Genetics Institute, University College London, London WC1E 6BT, UK.|Departamento de Tecnología Médica, Facultad de Ciencias de la Salud, Universidad de Tarapacá, Arica 1000009, Chile.
authors.forename: Macarena
authors.initials: M
authors.lastname: Fuentes-Guajardo
authors.affiliation: Centro Nacional Patagónico, CONICET, Unidad de Diversidad, Sistematica y Evolucion, Puerto Madryn U912OACD, Argentina.
authors.forename: Mirsha
authors.initials: M
authors.lastname: Quinto-Sánchez
authors.affiliation: Department of Genetics, Evolution and Environment, UCL Genetics Institute, University College London, London WC1E 6BT, UK.|Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima 31, Perú
authors.forename: Javier
authors.initials: J
authors.lastname: Mendoza-Revilla
authors.affiliation: Department of Genetics, Evolution and Environment, UCL Genetics Institute, University College London, London WC1E 6BT, UK.
authors.forename: Juan
authors.initials: J
authors.lastname: Camilo Chacón-Duque
authors.affiliation: Department of Genetics, Evolution and Environment, UCL Genetics Institute, University College London, London WC1E 6BT, UK.|Laboratorio de Genética Molecular, Escuela Nacional de Antropologia e Historia, México City 14030, México.
authors.forename: Victor
authors.initials: V
authors.lastname: Acuña-Alonzo
authors.affiliation: GENMOL (Genética Molecular), Universidad de Antioquia, Medellín 5001000, Colombia.
authors.forename: Claudia
authors.initials: C
authors.lastname: Jaramillo
authors.affiliation: GENMOL (Genética Molecular), Universidad de Antioquia, Medellín 5001000, Colombia.
authors.forename: William
authors.initials: W
authors.lastname: Arias
authors.affiliation: Laboratorio de Genética Molecular, Escuela Nacional de Antropologia e Historia, México City 14030, México.|Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM-Instituto Nacional de Medicina Genómica, México City 4510, México.
authors.forename: Rodrigo Barquera
authors.initials: RB
authors.lastname: Lozano
authors.affiliation: Laboratorio de Genética Molecular, Escuela Nacional de Antropologia e Historia, México City 14030, México.|Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM-Instituto Nacional de Medicina Genómica, México City 4510, México.
authors.forename: Gastón Macín
authors.initials: GM
authors.lastname: Pérez
authors.affiliation: Departamento de Anatomía, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), México City 04510, México.
authors.forename: Jorge
authors.initials: J
authors.lastname: Gómez-Valdés
authors.affiliation: Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM-Instituto Nacional de Medicina Genómica, México City 4510, México.
authors.forename: Hugo
authors.initials: H
authors.lastname: Villamil-Ramírez
authors.affiliation: Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brasil.
authors.forename: Tábita
authors.initials: T
authors.lastname: Hunemeier
authors.affiliation: Centro Nacional Patagónico, CONICET, Unidad de Diversidad, Sistematica y Evolucion, Puerto Madryn U912OACD, Argentina.|Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brasil.
authors.forename: Virginia
authors.initials: V
authors.lastname: Ramallo
authors.affiliation: Centro Nacional Patagónico, CONICET, Unidad de Diversidad, Sistematica y Evolucion, Puerto Madryn U912OACD, Argentina.|Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brasil.
authors.forename: Caio C
authors.initials: CC
authors.lastname: Silva de Cerqueira
authors.affiliation: Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima 31, Perú
authors.forename: Malena
authors.initials: M
authors.lastname: Hurtado
authors.affiliation: Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima 31, Perú
authors.forename: Valeria
authors.initials: V
authors.lastname: Villegas
authors.affiliation: Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima 31, Perú
authors.forename: Vanessa
authors.initials: V
authors.lastname: Granja
authors.affiliation: Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima 31, Perú
authors.forename: Carla
authors.initials: C
authors.lastname: Gallo
authors.affiliation: Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima 31, Perú
authors.forename: Giovanni
authors.initials: G
authors.lastname: Poletti
authors.affiliation: Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brasil.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Schuler-Faccini
authors.affiliation: Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brasil.
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Salzano
authors.affiliation: Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brasil.
authors.forename: Maria-Cátira
authors.initials: MC
authors.lastname: Bortolini
authors.affiliation: Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM-Instituto Nacional de Medicina Genómica, México City 4510, México.
authors.forename: Samuel
authors.initials: S
authors.lastname: Canizales-Quinteros
authors.affiliation: Division of Developmental Biology, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian EH25 9RG, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Cheeseman
authors.affiliation: Departamento de Antropología, Universidad de Antioquia, Medellín 5001000, Colombia.
authors.forename: Javier
authors.initials: J
authors.lastname: Rosique
authors.affiliation: GENMOL (Genética Molecular), Universidad de Antioquia, Medellín 5001000, Colombia.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bedoya
authors.affiliation: Instituto de Alta Investigación, Universidad de Tarapacá, Arica 1000000, Chile.
authors.forename: Francisco
authors.initials: F
authors.lastname: Rothhammer
authors.affiliation: Division of Developmental Biology, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian EH25 9RG, UK.
authors.forename: Denis
authors.initials: D
authors.lastname: Headon
authors.affiliation: Centro Nacional Patagónico, CONICET, Unidad de Diversidad, Sistematica y Evolucion, Puerto Madryn U912OACD, Argentina.
authors.forename: Rolando
authors.initials: R
authors.lastname: González-José
authors.affiliation: Department of Genetics, Evolution and Environment, UCL Genetics Institute, University College London, London WC1E 6BT, UK.|Schools of BioSciences and Mathematics and Statistics, University of Melbourne, Melbourne, Victoria 3010, Australia.
authors.forename: David
authors.identifier: 0000-0002-1480-6115
authors.initials: D
authors.lastname: Balding
authors.affiliation: Department of Genetics, Evolution and Environment, UCL Genetics Institute, University College London, London WC1E 6BT, UK.
authors.forename: Andrés
authors.initials: A
authors.lastname: Ruiz-Linares
mesh_terms: D000328:Adult; D063405:Anatomic Variation; D000818:Animals; D000070585:Cadherin Related Proteins / Q000235:genetics*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D053339:Edar Receptor / Q000235:genetics*; D005145:Face / Q000033:anatomy & histology*; D055106:Genome-Wide Association Study; D006801:Humans; D007843:Latin America; D008445:Maxillofacial Development / Q000235:genetics; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics*; D051761:Paired Box Transcription Factors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult; D000074290:Zinc Finger Protein Gli3 / Q000235:genetics*
chemical_list: D000070585:Cadherin Related Proteins; D050659:Core Binding Factor Alpha 1 Subunit; C000628284:DCHS2 protein, human; C506008:EDAR protein, human; D053339:Edar Receptor; C506009:Edar protein, mouse; C065683:GLI3 protein, human; D009419:Nerve Tissue Proteins; D051761:Paired Box Transcription Factors; C493709:RUNX2 protein, human; D000074290:Zinc Finger Protein Gli3; C070835:PAX1 transcription factor