Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment

ABSTRACT: The genetic basis of earlobe attachment has been a matter of debate since the early 20th century, such that geneticists argue both for and against polygenic inheritance. Recent genetic studies have identified a few loci associated with the trait, but large-scale analyses are still lacking. Here, we performed a genome-wide association study of lobe attachment in a multiethnic sample of 74,660 individuals from four cohorts (three with the trait scored by an expert rater and one with the trait self-reported). Meta-analysis of the three expertrater-scored cohorts revealed six associated loci harboring numerous candidate genes, including EDAR, SP5, MRPS22, ADGRG6 (GPR126), KIAA1217, and PAX9. The large self-reported 23andMe cohort recapitulated each of these six loci. Moreover, meta-analysis across all four cohorts revealed a total of 49 significant (p < 5 3 10 8 ) loci. Annotation and enrichment analyses of these 49 loci showed strong evidence of genes involved in ear development and syndromes with auricular phenotypes. RNA sequencing data from both human fetal ear and mouse second branchial arch tissue confirmed that genes located among associated loci showed evidence of expression. These results provide strong evidence for the polygenic nature of earlobe attachment and offer insights into the biological basis of normal and abnormal ear development.

• Autores: Shaffer, John; Li, Jinxi; Lee, Myoung Keun; Gallo, Carla; Poletti, Giovanni; Schuler Faccini, Lavinia; Bortolini, María Cátira; Canizales Quinteros, Samuel; Rothhammer, Francisco; Bedoya Berrío, Gabriel de Jesús; González José, Rolando; Pfeffer, Paige; Wollenschlaeger, Christopher; Hecht, Jacqueline; Wehby, George; Moreno Uribe, Lina María; Ding, Anan; Jin, Li; Yang, Yajun; Carlson, Jenna; Leslie, Elizabeth; Feingold, Eleanor; Marazita, Mary; Hinds, David; Cox, Timothy; Wang, Sijia; Ruiz Linares, Andrés; Weinberg, Seth
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2017
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/26749
• Acceso en línea: http://hdl.handle.net/10495/26749
• Palabra clave: Región Branquial - anatomía e histología; Branchial Region - anatomy & histology; Proteínas de Unión al ADN - genética; DNA-Binding Proteins - genetics; Oído - anatomía e histología; Ear - anatomy & histology; Estudio de Asociación del Genoma Completo; Genome-Wide Association Study; Genotipo; Genotype; Factor de Transcripción PAX9 - genética; PAX9 Transcription Factor - genetics; Sitios de Carácter Cuantitativo - genética; Quantitative Trait Loci - genetics; Receptores Acoplados a Proteínas G - genética; Receptors, G-Protein-Coupled - genetics
• Rights: openAccess
• License: http://creativecommons.org/licenses/by-nc-nd/2.5/co/