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Am J Hum Genet. 2017 Dec 7;101(6):913-924. doi: 10.1016/j.ajhg.2017.10.001. Epub 2017 Nov 30.

Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment.

Author information

1
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
2
Chinese Academy of Sciences Key Laboratory of Computational Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
3
Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA 15219, USA.
4
Department of Genetics, Evolution and Environment, University College London, London, UK.
5
23andMe Inc., 899 West Evelyn Avenue, Mountain View, CA 94041, USA.
6
Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, 430 Cercado de Lima, Peru.
7
Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre 90040-060, Brazil.
8
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, Universidad Nacional Autónoma de México, Instituto Nacional de Medicina Genómica, Mexico City 4510, Mexico.
9
Instituto de Alta Investigación, Universidad de Tarapacá, Arica, Chile; Facultad de Medicina, Universidad de Chile, Santiago 8320000, Chile.
10
Grupo Genética Molecular GENMOL, Universidad de Antioquia, Medellín 050003, Colombia.
11
Instituto Patagónico de Ciencias Sociales y Humanas, Centro Científico Tecnológico, Centro Nacional Patagónico, Consejo Nacional de Investigaciones Científicas y Técnicas, Puerto Madryn U9120, Argentina.
12
Center for Advanced Dental Education, Orthodontics Program, Saint Louis University, St. Louis, MO 63104, USA.
13
Department of Orthodontics, University of Pittsburgh, Pittsburgh, PA 15261, USA.
14
Department of Pediatrics, McGovern Medical School, University of Texas, Houston, TX 77030, USA.
15
Department of Health Management and Policy, University of Iowa, Iowa City, IA 52246, USA.
16
Department of Orthodontics, University of Iowa, Iowa City, IA 52242, USA.
17
Chinese Academy of Sciences Key Laboratory of Computational Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China.
18
Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China.
19
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA 15261, USA.
20
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA; Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA 15219, USA; Clinical and Translational Science Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
21
Center for Developmental Biology & Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA 98101, USA; Craniofacial Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA; Department of Anatomy & Developmental Biology, Monash University, Clayton, VIC 3800, Australia.
22
Chinese Academy of Sciences Key Laboratory of Computational Biology, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China. Electronic address: wangsijia@picb.ac.cn.
23
Department of Genetics, Evolution and Environment, University College London, London, UK; Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China; Laboratory of Biocultural Anthropology, Law, Ethics, and Health, Centre National de la Recherche Scientifique and Etablissement Français du Sang, UMR 7268, Aix-Marseille University, Marseille 13284, France.
24
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA; Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA 15219, USA; Department of Anthropology, University of Pittsburgh, Pittsburgh, PA 15260, USA. Electronic address: smwst46@pitt.edu.

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 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.

KEYWORDS:

attached earlobe; complex trait genetics; epistasis; genome-wide association study; multigenic; pharyngeal arch; pinna; trans-ethnic; unattached earlobe

PMID:
29198719
PMCID:
PMC5812923
DOI:
10.1016/j.ajhg.2017.10.001
[Indexed for MEDLINE]
Free PMC Article

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