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
epublish 2012/09/13
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:
ISSNTYPE:
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
Cites Am J Phys Anthropol. 2006 Oct;131(2):169-80 16552732
Cites J Hum Genet. 2006;51(8):721-6 16865294
Cites Anat Rec A Discov Mol Cell Evol Biol. 2006 Dec;288(12):1225-33 17075844
Cites Twin Res Hum Genet. 2006 Dec;9(6):899-906 17254428
Cites Cell Cycle. 2007 Feb 1;6(3):262-8 17224651
Cites Br J Dermatol. 2007 May;156(5):861-70 17263807
Cites Hum Brain Mapp. 2007 Jun;28(6):502-18 17469173
Cites Bioinformatics. 2007 May 15;23(10):1294-6 17384015
Cites Biochim Biophys Acta. 2007 Jun;1773(6):814-20 17467076
Cites Am J Phys Anthropol. 2007 Nov;134(3):312-22 17632793
Cites Eur J Epidemiol. 2007;22(11):819-29 17955331
Cites Eur J Med Genet. 2008 Jan-Feb;51(1):44-53 18054308
Cites Am J Hum Genet. 2008 Feb;82(2):411-23 18252221
Cites J Clin Invest. 2008 Jun;118(6):2076-87 18483623
Cites Dev Biol. 2008 Sep 1;321(1):273-82 18634775
Cites Nat Genet. 2008 Nov;40(11):1341-7 18836445
Cites Am J Hum Biol. 2009 Jan-Feb;21(1):36-47 18663742
Cites Curr Biol. 2009 Mar 10;19(5):R192-3 19278628
Cites Nat Genet. 2009 Apr;41(4):473-7 19270707
Cites Rofo. 2009 Aug;181(8):748-59 19598074
Cites J Hum Evol. 2009 Aug;57(2):179-90 19604539
Cites Neuroimage. 2009 Oct 15;48(1):37-49 19446645
Cites J Med Genet. 2009 Sep;46(9):614-6 19508968
Cites Am J Phys Anthropol. 2009 Oct;140(2):205-15 19418568
Cites Orthod Craniofac Res. 2009 Nov;12(4):271-81 19840279
Cites Nat Genet. 2010 Jan;42(1):24-6 20023658
Cites Am J Med Genet C Semin Med Genet. 2010 Feb 15;154C(1):133-41 20104608
Cites Hum Mol Genet. 2010 Mar 1;19(5):774-89 20007998
Cites Hum Mutat. 2010 Apr;31(4):391-406 20127975
Cites PLoS Genet. 2010 May;6(5):e1000934 20463881
Cites J Hum Evol. 2010 May;58(5):424-31 20378153
Cites Nat Genet. 2010 Jun;42(6):525-9 20436469
Cites Nat Genet. 2010 Oct;42(10):902-5 20835236
Cites Nature. 2010 Oct 14;467(7317):832-8 20881960
Cites Nat Rev Genet. 2011 Mar;12(3):179-92 21331090
Cites Hum Genet. 2011 Apr;129(4):443-54 21197618
Cites Int J Epidemiol. 2011 Apr;40(2):294-307 20167617
Cites Forensic Sci Int Genet. 2011 Jun;5(3):170-80 20457092
Cites PLoS One. 2011;6(5):e20241 21655288
Cites Eur J Epidemiol. 2011 Aug;26(8):657-86 21877163
Cites Eur J Hum Genet. 2011 Nov;19(11):1192-7 21694738
Cites Horm Behav. 2011 Nov;60(5):681-90 21983236
Cites Eur J Epidemiol. 2011 Oct;26(10):811-24 22002080
Cites Am J Phys Anthropol. 2011 Sep;146(1):83-93 21710659
Cites Proc Natl Acad Sci U S A. 2011 Dec 6;108(49):19546-51 22106280
Cites J Clin Endocrinol Metab. 2012 Jan;97(1):E145-50 22013104
Cites Am J Hum Genet. 2012 Mar 9;90(3):478-85 22341974
Cites PLoS One. 2012;7(5):e34861 22567092
Cites Soz Praventivmed. 2001;46(3):186-94 11565448
Cites Nat Genet. 2002 Jan;30(1):97-101 11731797
Cites Syst Biol. 2001 Feb;50(1):141-9 12116591
Cites Am J Phys Anthropol. 2002;Suppl 35:63-91 12653309
Cites Biometrics. 1982 Jun;38(2):341-50 6810969
Cites Q Rev Biol. 1983 Mar;58(1):1-28 6346380
Cites Am J Phys Anthropol. 1983 Oct;62(2):151-65 6650677
Cites Eur J Epidemiol. 1991 Jul;7(4):403-22 1833235
Cites Am J Phys Anthropol. 1991 Nov;86(3):415-27 1746646
Cites Am J Orthod Dentofacial Orthop. 1993 Aug;104(2):121-31 8338064
Cites Nat Genet. 1996 Feb;12(2):124-9 8563748
Cites Angle Orthod. 1998 Oct;68(5):467-70 9770105
Cites Am J Orthod Dentofacial Orthop. 2005 Feb;127(2):200-7; quiz 260-1 15750539
Cites Semin Fetal Neonatal Med. 2005 Jun;10(3):243-57 15927879
Cites Orthod Craniofac Res. 2006 Feb;9(1):18-30 16420271
Cites J Med Genet. 2006 Jun;43(6):e28 16740912
Cites Nat Genet. 2006 Aug;38(8):904-9 16862161
GRANTS
GRANTID AGENCY COUNTRY
1R01EY018246 NEI NIH HHS United States
G20234 Biotechnology and Biological Sciences Research Council United Kingdom
HD50735 NICHD NIH HHS United States
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
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 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
OTHERID SOURCE
PMC3441666 NLM