Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment

John R. Shaffer, Jinxi Li, Myoung Keun Lee, Jasmien Roosenboom, Ekaterina Orlova, Kaustabh Adhikari, Carla Gallo, Giovanni Poletti, Lavinia Schuler-Faccini, Maria Cátira Bortolini, Samuel Canizales-Quinteros, Francisco Rothhammer, Gabriel Bedoya, Rolando González-José, Paige E. Pfeffer, Christopher A. Wollenschlaeger, Jacqueline T. Hecht, George L. Wehby, Lina M. Moreno, Anan Ding & 11 others Li Jin, Yajun Yang, Jenna C. Carlson, Elizabeth J. Leslie, Eleanor Feingold, Mary L. Marazita, David A. Hinds, Timothy C. Cox, Sijia Wang, Andrés Ruiz-Linares, Seth M. Weinberg

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)913-924
Number of pages12
JournalAmerican Journal of Human Genetics
Volume101
Issue number6
DOIs
Publication statusPublished - 7 Dec 2017

Keywords

  • Attached earlobe
  • Complex trait genetics
  • Epistasis
  • Genome-wide association study
  • Multigenic
  • Pharyngeal arch
  • Pinna
  • Trans-ethnic
  • Unattached earlobe

Cite this

Shaffer, J. R., Li, J., Lee, M. K., Roosenboom, J., Orlova, E., Adhikari, K., ... Weinberg, S. M. (2017). Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment. American Journal of Human Genetics, 101(6), 913-924. https://doi.org/10.1016/j.ajhg.2017.10.001
Shaffer, John R. ; Li, Jinxi ; Lee, Myoung Keun ; Roosenboom, Jasmien ; Orlova, Ekaterina ; Adhikari, Kaustabh ; Gallo, Carla ; Poletti, Giovanni ; Schuler-Faccini, Lavinia ; Bortolini, Maria Cátira ; Canizales-Quinteros, Samuel ; Rothhammer, Francisco ; Bedoya, Gabriel ; González-José, Rolando ; Pfeffer, Paige E. ; Wollenschlaeger, Christopher A. ; Hecht, Jacqueline T. ; Wehby, George L. ; Moreno, Lina M. ; Ding, Anan ; Jin, Li ; Yang, Yajun ; Carlson, Jenna C. ; Leslie, Elizabeth J. ; Feingold, Eleanor ; Marazita, Mary L. ; Hinds, David A. ; Cox, Timothy C. ; Wang, Sijia ; Ruiz-Linares, Andrés ; Weinberg, Seth M. / Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment. In: American Journal of Human Genetics. 2017 ; Vol. 101, No. 6. pp. 913-924.
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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.",
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Shaffer, JR, Li, J, Lee, MK, Roosenboom, J, Orlova, E, Adhikari, K, Gallo, C, Poletti, G, Schuler-Faccini, L, Bortolini, MC, Canizales-Quinteros, S, Rothhammer, F, Bedoya, G, González-José, R, Pfeffer, PE, Wollenschlaeger, CA, Hecht, JT, Wehby, GL, Moreno, LM, Ding, A, Jin, L, Yang, Y, Carlson, JC, Leslie, EJ, Feingold, E, Marazita, ML, Hinds, DA, Cox, TC, Wang, S, Ruiz-Linares, A & Weinberg, SM 2017, 'Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment' American Journal of Human Genetics, vol. 101, no. 6, pp. 913-924. https://doi.org/10.1016/j.ajhg.2017.10.001

Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment. / Shaffer, John R.; Li, Jinxi; Lee, Myoung Keun; Roosenboom, Jasmien; Orlova, Ekaterina; Adhikari, Kaustabh; Gallo, Carla; Poletti, Giovanni; Schuler-Faccini, Lavinia; Bortolini, Maria Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; González-José, Rolando; Pfeffer, Paige E.; Wollenschlaeger, Christopher A.; Hecht, Jacqueline T.; Wehby, George L.; Moreno, Lina M.; Ding, Anan; Jin, Li; Yang, Yajun; Carlson, Jenna C.; Leslie, Elizabeth J.; Feingold, Eleanor; Marazita, Mary L.; Hinds, David A.; Cox, Timothy C.; Wang, Sijia; Ruiz-Linares, Andrés; Weinberg, Seth M.

In: American Journal of Human Genetics, Vol. 101, No. 6, 07.12.2017, p. 913-924.

Research output: Contribution to journalArticleResearchpeer-review

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

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DO - 10.1016/j.ajhg.2017.10.001

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JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

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Shaffer JR, Li J, Lee MK, Roosenboom J, Orlova E, Adhikari K et al. Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment. American Journal of Human Genetics. 2017 Dec 7;101(6):913-924. https://doi.org/10.1016/j.ajhg.2017.10.001