A genome-wide association study identifies five loci influencing facial morphology in Europeans.
Inter-individual variation in facial shape is one of the most noticeable phenotypes in humans, and it is clearly under genetic regulation; however, almost nothing is known about the genetic basis of normal human facial morphology. We therefore conducted a genome-wide association study for facial sha...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2012-09-01
|
Series: | PLoS Genetics |
Online Access: | http://europepmc.org/articles/PMC3441666?pdf=render |
id |
doaj-06abf74d128b48468ca0ac2ca25ea53e |
---|---|
record_format |
Article |
spelling |
doaj-06abf74d128b48468ca0ac2ca25ea53e2020-11-25T01:04:30ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042012-09-0189e100293210.1371/journal.pgen.1002932A genome-wide association study identifies five loci influencing facial morphology in Europeans.Fan LiuFedde van der LijnClaudia SchurmannGu ZhuM Mallar ChakravartyPirro G HysiAndreas WollsteinOscar LaoMarleen de BruijneM Arfan IkramAad van der LugtFernando RivadeneiraAndré G UitterlindenAlbert HofmanWiro J NiessenGeorg HomuthGreig de ZubicarayKatie L McMahonPaul M ThompsonAmro DaboulRalf PulsKatrin HegenscheidLiisa BevanZdenka PausovaSarah E MedlandGrant W MontgomeryMargaret J WrightCarol WickingStefan BoehringerTimothy D SpectorTomáš PausNicholas G MartinReiner BiffarManfred KayserInter-individual variation in facial shape is one of the most noticeable phenotypes in humans, and it is clearly under genetic regulation; however, almost nothing is known about the genetic basis of normal human facial morphology. We therefore conducted a genome-wide association study for facial shape phenotypes in multiple discovery and replication cohorts, considering almost ten thousand individuals of European descent from several countries. Phenotyping of facial shape features was based on landmark data obtained from three-dimensional head magnetic resonance images (MRIs) and two-dimensional portrait images. We identified five independent genetic loci associated with different facial phenotypes, suggesting the involvement of five candidate genes--PRDM16, PAX3, TP63, C5orf50, and COL17A1--in the determination of the human face. Three of them have been implicated previously in vertebrate craniofacial development and disease, and the remaining two genes potentially represent novel players in the molecular networks governing facial development. Our finding at PAX3 influencing the position of the nasion replicates a recent GWAS of facial features. In addition to the reported GWA findings, we established links between common DNA variants previously associated with NSCL/P at 2p21, 8q24, 13q31, and 17q22 and normal facial-shape variations based on a candidate gene approach. Overall our study implies that DNA variants in genes essential for craniofacial development contribute with relatively small effect size to the spectrum of normal variation in human facial morphology. This observation has important consequences for future studies aiming to identify more genes involved in the human facial morphology, as well as for potential applications of DNA prediction of facial shape such as in future forensic applications.http://europepmc.org/articles/PMC3441666?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fan Liu Fedde van der Lijn Claudia Schurmann Gu Zhu M Mallar Chakravarty Pirro G Hysi Andreas Wollstein Oscar Lao Marleen de Bruijne M Arfan Ikram Aad van der Lugt Fernando Rivadeneira André G Uitterlinden Albert Hofman Wiro J Niessen Georg Homuth Greig de Zubicaray Katie L McMahon Paul M Thompson Amro Daboul Ralf Puls Katrin Hegenscheid Liisa Bevan Zdenka Pausova Sarah E Medland Grant W Montgomery Margaret J Wright Carol Wicking Stefan Boehringer Timothy D Spector Tomáš Paus Nicholas G Martin Reiner Biffar Manfred Kayser |
spellingShingle |
Fan Liu Fedde van der Lijn Claudia Schurmann Gu Zhu M Mallar Chakravarty Pirro G Hysi Andreas Wollstein Oscar Lao Marleen de Bruijne M Arfan Ikram Aad van der Lugt Fernando Rivadeneira André G Uitterlinden Albert Hofman Wiro J Niessen Georg Homuth Greig de Zubicaray Katie L McMahon Paul M Thompson Amro Daboul Ralf Puls Katrin Hegenscheid Liisa Bevan Zdenka Pausova Sarah E Medland Grant W Montgomery Margaret J Wright Carol Wicking Stefan Boehringer Timothy D Spector Tomáš Paus Nicholas G Martin Reiner Biffar Manfred Kayser A genome-wide association study identifies five loci influencing facial morphology in Europeans. PLoS Genetics |
author_facet |
Fan Liu Fedde van der Lijn Claudia Schurmann Gu Zhu M Mallar Chakravarty Pirro G Hysi Andreas Wollstein Oscar Lao Marleen de Bruijne M Arfan Ikram Aad van der Lugt Fernando Rivadeneira André G Uitterlinden Albert Hofman Wiro J Niessen Georg Homuth Greig de Zubicaray Katie L McMahon Paul M Thompson Amro Daboul Ralf Puls Katrin Hegenscheid Liisa Bevan Zdenka Pausova Sarah E Medland Grant W Montgomery Margaret J Wright Carol Wicking Stefan Boehringer Timothy D Spector Tomáš Paus Nicholas G Martin Reiner Biffar Manfred Kayser |
author_sort |
Fan Liu |
title |
A genome-wide association study identifies five loci influencing facial morphology in Europeans. |
title_short |
A genome-wide association study identifies five loci influencing facial morphology in Europeans. |
title_full |
A genome-wide association study identifies five loci influencing facial morphology in Europeans. |
title_fullStr |
A genome-wide association study identifies five loci influencing facial morphology in Europeans. |
title_full_unstemmed |
A genome-wide association study identifies five loci influencing facial morphology in Europeans. |
title_sort |
genome-wide association study identifies five loci influencing facial morphology in europeans. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2012-09-01 |
description |
Inter-individual variation in facial shape is one of the most noticeable phenotypes in humans, and it is clearly under genetic regulation; however, almost nothing is known about the genetic basis of normal human facial morphology. We therefore conducted a genome-wide association study for facial shape phenotypes in multiple discovery and replication cohorts, considering almost ten thousand individuals of European descent from several countries. Phenotyping of facial shape features was based on landmark data obtained from three-dimensional head magnetic resonance images (MRIs) and two-dimensional portrait images. We identified five independent genetic loci associated with different facial phenotypes, suggesting the involvement of five candidate genes--PRDM16, PAX3, TP63, C5orf50, and COL17A1--in the determination of the human face. Three of them have been implicated previously in vertebrate craniofacial development and disease, and the remaining two genes potentially represent novel players in the molecular networks governing facial development. Our finding at PAX3 influencing the position of the nasion replicates a recent GWAS of facial features. In addition to the reported GWA findings, we established links between common DNA variants previously associated with NSCL/P at 2p21, 8q24, 13q31, and 17q22 and normal facial-shape variations based on a candidate gene approach. Overall our study implies that DNA variants in genes essential for craniofacial development contribute with relatively small effect size to the spectrum of normal variation in human facial morphology. This observation has important consequences for future studies aiming to identify more genes involved in the human facial morphology, as well as for potential applications of DNA prediction of facial shape such as in future forensic applications. |
url |
http://europepmc.org/articles/PMC3441666?pdf=render |
work_keys_str_mv |
AT fanliu agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT feddevanderlijn agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT claudiaschurmann agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT guzhu agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT mmallarchakravarty agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT pirroghysi agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT andreaswollstein agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT oscarlao agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT marleendebruijne agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT marfanikram agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT aadvanderlugt agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT fernandorivadeneira agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT andreguitterlinden agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT alberthofman agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT wirojniessen agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT georghomuth agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT greigdezubicaray agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT katielmcmahon agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT paulmthompson agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT amrodaboul agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT ralfpuls agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT katrinhegenscheid agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT liisabevan agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT zdenkapausova agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT sarahemedland agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT grantwmontgomery agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT margaretjwright agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT carolwicking agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT stefanboehringer agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT timothydspector agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT tomaspaus agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT nicholasgmartin agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT reinerbiffar agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT manfredkayser agenomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT fanliu genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT feddevanderlijn genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT claudiaschurmann genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT guzhu genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT mmallarchakravarty genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT pirroghysi genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT andreaswollstein genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT oscarlao genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT marleendebruijne genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT marfanikram genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT aadvanderlugt genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT fernandorivadeneira genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT andreguitterlinden genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT alberthofman genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT wirojniessen genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT georghomuth genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT greigdezubicaray genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT katielmcmahon genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT paulmthompson genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT amrodaboul genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT ralfpuls genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT katrinhegenscheid genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT liisabevan genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT zdenkapausova genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT sarahemedland genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT grantwmontgomery genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT margaretjwright genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT carolwicking genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT stefanboehringer genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT timothydspector genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT tomaspaus genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT nicholasgmartin genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT reinerbiffar genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans AT manfredkayser genomewideassociationstudyidentifiesfivelociinfluencingfacialmorphologyineuropeans |
_version_ |
1725197590394306560 |