Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment

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 expert-rater-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 × 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.Fil: Shaffer, John R.. University of Pittsburgh; Estados UnidosFil: Li, Jinxi. University of Chinese Academy of Sciences; ChinaFil: Lee, Myoung Keun. University of Pittsburgh; Estados UnidosFil: Roosenboom, Jasmien. University of Pittsburgh; Estados UnidosFil: Orlova, Ekaterina. University of Pittsburgh; Estados UnidosFil: Adhikari, Kaustabh. Colegio Universitario de Londres; Reino UnidoFil: Gallo, Carla. Universidad Peruana Cayetano Heredia; PerúFil: Poletti, Giovanni. Universidad Peruana Cayetano Heredia; PerúFil: Schuler Faccini, Lavinia. Universidade Federal do Rio Grande do Sul; BrasilFil: Bortolini, Maria Catira. Universidade Federal do Rio Grande do Sul; BrasilFil: Canizales Quinteros, Samuel. Universidad Nacional Autónoma de México; MéxicoFil: Rothhammer, Francisco. Universidad de Tarapacá; ChileFil: Bedoya, Gabriel. Universidad de Antioquia; ColombiaFil: González José, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; ArgentinaFil: Pfeffer, Paige E.. Saint Louis University; Estados UnidosFil: Wollenschlaeger, Christopher A.. University of Pittsburgh; Estados UnidosFil: Hecht, Jacqueline T.. University of Texas; Estados UnidosFil: Wehby, George. University of Iowa; Estados UnidosFil: Moreno, Lina M.. University of Iowa; Estados UnidosFil: Ding, Anan. University of Chinese Academy of Sciences; ChinaFil: Jin, Li. University of Chinese Academy of Sciences; China. Fudan University; ChinaFil: Yang, Yajun. Fudan University; ChinaFil: Carlson, Jenna C.. University of Pittsburgh; Estados UnidosFil: Leslie, Elizabeth J.. University of Pittsburgh; Estados UnidosFil: Feingold, Eleanor. University of Pittsburgh; Estados UnidosFil: Marazita, Mary L.. University of Pittsburgh; Estados UnidosFil: Hinds, David A.. 899 West Evelyn Avenue; Estados UnidosFil: Cox, Timothy C.. Seattle Children’s Research Institute; Estados Unidos. University of Washington; Estados Unidos. Monash University; AustraliaFil: Wang, Sijia. University of Chinese Academy of Sciences; China. Fudan University; ChinaFil: Ruiz Linares, Andrés. Colegio Universitario de Londres; Reino Unido. Fudan University; China. Aix-Marseille University; FranciaFil: Weinberg, Seth M.. University of Pittsburgh; Estados Unido

Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment

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