Shaffer, JR;
Li, J;
Lee, MK;
Roosenboom, J;
Orlova, E;
Adhikari, K;
Gallo, C;
... Weinberg, SM; + view all
(2017)
Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment.
American Journal of Human Genetics
, 101
(6)
pp. 913-924.
10.1016/j.ajhg.2017.10.001.
Preview |
Text (Published article with supplementary information)
Shaffer_Multiethnic_GWAS.pdf - Published Version Download (4MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ajhg.2017.10.001 |
| Publisher version: | https://doi.org/10.1016/j.ajhg.2017.10.001 |
| Language: | English |
| Additional information: | Copyright © 2017 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | pinna, genome-wide association study, trans-ethnic, pharyngeal arch, complex trait genetics, multigenic, attached earlobe, unattached earlobe, epistasis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10041330 |
Archive Staff Only
 |
View Item |
