TY - JOUR
T1 - Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment
AU - Shaffer, John R.
AU - Li, Jinxi
AU - Lee, Myoung Keun
AU - Roosenboom, Jasmien
AU - Orlova, Ekaterina
AU - Adhikari, Kaustabh
AU - Gallo, Carla
AU - Poletti, Giovanni
AU - Schuler-Faccini, Lavinia
AU - Bortolini, Maria Cátira
AU - Canizales-Quinteros, Samuel
AU - Rothhammer, Francisco
AU - Bedoya, Gabriel
AU - González-José, Rolando
AU - Pfeffer, Paige E.
AU - Wollenschlaeger, Christopher A.
AU - Hecht, Jacqueline T.
AU - Wehby, George L.
AU - Moreno, Lina M.
AU - Ding, Anan
AU - Jin, Li
AU - Yang, Yajun
AU - Carlson, Jenna C.
AU - Leslie, Elizabeth J.
AU - Feingold, Eleanor
AU - Marazita, Mary L.
AU - Hinds, David A.
AU - Cox, Timothy C.
AU - Wang, Sijia
AU - Ruiz-Linares, Andrés
AU - Weinberg, Seth M.
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
UR - https://www.scopus.com/pages/publications/85035787162
U2 - 10.1016/j.ajhg.2017.10.001
DO - 10.1016/j.ajhg.2017.10.001
M3 - Article
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 -