Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment

Francisco Rothhammer; 23andMe Research Team

doi:10.1016/j.ajhg.2017.10.001

Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment

Título traducido de la contribución: Un GWAS multiétnico revela la arquitectura poligénica de la inserción del lóbulo de la oreja

Francisco Rothhammer
, 23andMe Research Team

Instituto de Alta Investigación

Universidad de Chile

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

31 Citas (Scopus)

Resumen

La base genética de la unión del lóbulo de la oreja ha sido un tema de debate desde principios del siglo XX, de modo que los genetistas argumentan tanto a favor como en contra de la herencia poligénica. Estudios genéticos recientes han identificado algunos loci asociados con el rasgo, pero aún faltan análisis a gran escala. Aquí, realizamos un estudio de asociación de todo el genoma de la unión del lóbulo en una muestra multiétnica de 74.660 individuos de cuatro cohortes (tres con el rasgo puntuado por un evaluador experto y uno con el rasgo autoinformado). El metaanálisis de las tres cohortes puntuadas por el evaluador experto reveló seis loci asociados que albergan numerosos genes candidatos, incluidos EDAR, SP5, MRPS22, ADGRG6 (GPR126), KIAA1217 y PAX9. La gran cohorte autoinformada de 23andMe recapituló cada uno de estos seis loci. Además, el metaanálisis en las cuatro cohortes reveló un total de 49 loci significativos (p < 5 × 10⁻⁸). Los análisis de anotación y enriquecimiento de estos 49 loci mostraron una sólida evidencia de genes implicados en el desarrollo del oído y síndromes con fenotipos auriculares. Los datos de secuenciación de ARN, tanto del oído fetal humano como del tejido del segundo arco branquial de ratón, confirmaron que los genes ubicados entre loci asociados mostraban evidencia de expresión. Estos resultados proporcionan una sólida evidencia de la naturaleza poligénica de la inserción del lóbulo auricular y ofrecen información sobre la base biológica del desarrollo normal y anormal del oído.

Título traducido de la contribución	Un GWAS multiétnico revela la arquitectura poligénica de la inserción del lóbulo de la oreja
Idioma original	Inglés
Páginas (desde-hasta)	913-924
Número de páginas	12
Publicación	American Journal of Human Genetics
Volumen	101
N.º	6
DOI	https://doi.org/10.1016/j.ajhg.2017.10.001
Estado	Publicada - 7 dic. 2017

Palabras clave

Lóbulo de la oreja adherido
Genética de rasgos complejos
Epistasis
Estudio de asociación de todo el genoma
Multigénico
Arco faríngeo
Pabellón auricular
Transétnico
Lóbulo de la oreja no adherido

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10.1016/j.ajhg.2017.10.001

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@article{b6a06dc60be34d508ac007959baa6a6a,

title = "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 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, L{\'o}bulo de la oreja adherido, Gen{\'e}tica de rasgos complejos, Epistasis, Estudio de asociaci{\'o}n de todo el genoma, Multig{\'e}nico, Arco far{\'i}ngeo, Pabell{\'o}n auricular, Trans{\'e}tnico, L{\'o}bulo de la oreja no adherido",

author = "Francisco Rothhammer and \{23andMe Research Team\}",

note = "Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2017",

month = dec,

day = "7",

doi = "10.1016/j.ajhg.2017.10.001",

language = "English",

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journal = "American Journal of Human Genetics",

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T1 - Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment

AU - Rothhammer, Francisco

AU - 23andMe Research Team

PY - 2017/12/7

Y1 - 2017/12/7

N2 - 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.

AB - 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.

KW - Attached earlobe

KW - Complex trait genetics

KW - Epistasis

KW - Genome-wide association study

KW - Multigenic

KW - Pharyngeal arch

KW - Pinna

KW - Trans-ethnic

KW - Unattached earlobe

KW - Lóbulo de la oreja adherido

KW - Genética de rasgos complejos

KW - Epistasis

KW - Estudio de asociación de todo el genoma

KW - Multigénico

KW - Arco faríngeo

KW - Pabellón auricular

KW - Transétnico

KW - Lóbulo de la oreja no adherido

UR - https://www.scopus.com/pages/publications/85035787162

UR - https://pubmed.ncbi.nlm.nih.gov/29198719/

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DO - 10.1016/j.ajhg.2017.10.001

M3 - Article

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AN - SCOPUS:85035787162

SN - 0002-9297

VL - 101

SP - 913

EP - 924

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 6

ER -

Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment

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