Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
23028347
TITLE
A genome-wide association study identifies five loci influencing facial morphology in Europeans.
ABSTRACT
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.
DATE PUBLISHED
2012 Sep
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/01/04
accepted 2012/07/13
entrez 2012/10/03 06:00
pubmed 2012/10/03 06:00
medline 2013/01/05 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Liu F Liu Fan F Department of Forensic Molecular Biology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
van der Lijn F van der Lijn Fedde F
Schurmann C Schurmann Claudia C
Zhu G Zhu Gu G
Chakravarty MM Chakravarty M Mallar MM
Hysi PG Hysi Pirro G PG
Wollstein A Wollstein Andreas A
Lao O Lao Oscar O
de Bruijne M de Bruijne Marleen M
Ikram MA Ikram M Arfan MA
van der Lugt A van der Lugt Aad A
Rivadeneira F Rivadeneira Fernando F
Uitterlinden AG Uitterlinden André G AG
Hofman A Hofman Albert A
Niessen WJ Niessen Wiro J WJ
Homuth G Homuth Georg G
de Zubicaray G de Zubicaray Greig G
McMahon KL McMahon Katie L KL
Thompson PM Thompson Paul M PM
Daboul A Daboul Amro A
Puls R Puls Ralf R
Hegenscheid K Hegenscheid Katrin K
Bevan L Bevan Liisa L
Pausova Z Pausova Zdenka Z
Medland SE Medland Sarah E SE
Montgomery GW Montgomery Grant W GW
Wright MJ Wright Margaret J MJ
Wicking C Wicking Carol C
Boehringer S Boehringer Stefan S
Spector TD Spector Timothy D TD
Paus T Paus Tomáš T
Martin NG Martin Nicholas G NG
Biffar R Biffar Reiner R
Kayser M Kayser Manfred M
INVESTIGATORS
JOURNAL
VOLUME: 8
ISSUE: 9
TITLE: PLoS genetics
ISOABBREVIATION: PLoS Genet
YEAR: 2012
MONTH: Sep
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1553-7404
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: PLoS Genet
COUNTRY: United States
ISSNLINKING: 1553-7390
NLMUNIQUEID: 101239074
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
R01 EY018246 NEI NIH HHS United States
1R01EY018246 NEI NIH HHS United States
HD50735 NICHD NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
G20234 Biotechnology and Biological Sciences Research Council United Kingdom
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Autoantigens genetics
Body Patterning genetics
DNA-Binding Proteins genetics
European Continental Ancestry Group genetics
Face anatomy & histology
Genome-Wide Association Study anatomy & histology
Humans anatomy & histology
Imaging, Three-Dimensional anatomy & histology
Magnetic Resonance Imaging anatomy & histology
Non-Fibrillar Collagens genetics
PAX3 Transcription Factor genetics
Paired Box Transcription Factors genetics
Phenotype genetics
Polymorphism, Single Nucleotide genetics
Transcription Factors genetics
Tumor Suppressor Proteins genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Autoantigens
0 DNA-Binding Proteins
0 Non-Fibrillar Collagens
0 PAX3 Transcription Factor
0 PAX3 protein, human
0 PRDM16 protein, human
0 Paired Box Transcription Factors
0 TP63 protein, human
0 Transcription Factors
0 Tumor Suppressor Proteins
0 collagen type XVII
OTHER ID's
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