Journal article
Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment
American journal of human genetics, Vol.101(6), pp.913-924
12/07/2017
DOI: 10.1016/j.ajhg.2017.10.001
PMCID: PMC5812923
PMID: 29198719
Abstract
The genetic basis of earlobe attachment has been a matter of debate since the early 20
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
) 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.
Details
- Title: Subtitle
- Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment
- Creators
- John R Shaffer - Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USAJinxi Li - 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, ChinaMyoung Keun Lee - Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA 15219, USAJasmien Roosenboom - Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA 15219, USAEkaterina Orlova - Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USAKaustabh Adhikari - Department of Genetics, Evolution and Environment, University College London, London, UKCarla Gallo - Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, 430 Cercado de Lima, PeruGiovanni Poletti - Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, 430 Cercado de Lima, PeruLavinia Schuler-Faccini - Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre 90040-060, BrazilMaria-Cátira Bortolini - Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre 90040-060, BrazilSamuel Canizales-Quinteros - 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, MexicoFrancisco Rothhammer - Instituto de Alta Investigación, Universidad de Tarapacá, Arica, Chile; Facultad de Medicina, Universidad de Chile, Santiago 8320000, ChileGabriel Bedoya - Grupo Genética Molecular GENMOL, Universidad de Antioquia, Medellín 050003, ColombiaRolando González-José - Instituto Patagónico de Ciencias Sociales y Humanas, Centro Científico Tecnológico, Centro Nacional Patagónico, Consejo Nacional de Investigaciones Científicas y Técnicas, Puerto Madryn U9120, ArgentinaPaige E Pfeffer - Center for Advanced Dental Education, Orthodontics Program, Saint Louis University, St. Louis, MO 63104, USAChristopher A Wollenschlaeger - Department of Orthodontics, University of Pittsburgh, Pittsburgh, PA 15261, USAJacqueline T Hecht - Department of Pediatrics, McGovern Medical School, University of Texas, Houston, TX 77030, USAGeorge L Wehby - Department of Health Management and Policy, University of Iowa, Iowa City, IA 52246, USALina M Moreno - Department of Orthodontics, University of Iowa, Iowa City, IA 52242, USAAnan Ding - 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, ChinaLi Jin - 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, ChinaYajun Yang - Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, ChinaJenna C Carlson - 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, USAElizabeth J Leslie - Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA 15219, USAEleanor Feingold - 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, USAMary L Marazita - 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, USADavid A Hinds - 23andMe Inc., 899 West Evelyn Avenue, Mountain View, CA 94041, USATimothy C Cox - 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, AustraliaSijia Wang - 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.cnAndrés Ruiz-Linares - 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, FranceSeth M Weinberg - 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
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.101(6), pp.913-924
- DOI
- 10.1016/j.ajhg.2017.10.001
- PMID
- 29198719
- PMCID
- PMC5812923
- NLM abbreviation
- Am J Hum Genet
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Publisher
- United States
- Grant note
- R01 DE022561 / NIDCR NIH HHS R01 DE027023 / NIDCR NIH HHS R01 DE016148 / NIDCR NIH HHS R00 DE025060 / NIDCR NIH HHS U01 DE020078 / NIDCR NIH HHS U01 DE020057 / NIDCR NIH HHS K22 LM011938 / NLM NIH HHS
- Language
- English
- Date published
- 12/07/2017
- Academic Unit
- Preventive and Community Dentistry; Orthodontics; Health Management and Policy; Economics; Craniofacial Anomalies Research Center; Public Policy Center (Archive); Dental Research
- Record Identifier
- 9984065992602771
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