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| PMID |
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| TITLE |
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| Novel genetic loci affecting facial shape variation in humans. |
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| ABSTRACT |
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| The human face represents a combined set of highly heritable phenotypes, but knowledge on its genetic architecture remains limited, despite the relevance for various fields. A series of genome-wide association studies on 78 facial shape phenotypes quantified from 3-dimensional facial images of 10,115 Europeans identified 24 genetic loci reaching study-wide suggestive association (p < 5 × 10 ), among which 17 were previously unreported. A follow-up multi-ethnic study in additional 7917 individuals confirmed 10 loci including six unreported ones (padjusted < 2.1 × 10 ). A global map of derived polygenic face scores assembled facial features in major continental groups consistent with anthropological knowledge. Analyses of epigenomic datasets from cranial neural crest cells revealed abundant -regulatory activities at the face-associated genetic loci. Luciferase reporter assays in neural crest progenitor cells highlighted enhancer activities of several face-associated DNA variants. These results substantially advance our understanding of the genetic basis underlying human facial variation and provide candidates for future in-vivo functional studies. |
| © 2019, Xiong et al. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2019/07/03 |
| accepted |
2019/11/22 |
| pubmed |
2019/11/26 06:00 |
| medline |
2020/05/12 06:00 |
| entrez |
2019/11/26 06:00 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Xiong Z |
|
Xiong |
Ziyi |
Z |
|
CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, University of Chinese Academy of Sciences (CAS), Beijing, China. |
| Dankova G |
|
Dankova |
Gabriela |
G |
|
Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands. |
| Howe LJ |
|
Howe |
Laurence J |
LJ |
|
Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, United Kingdom. |
| Lee MK |
|
Lee |
Myoung Keun |
MK |
|
Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, United States. |
| Hysi PG |
|
Hysi |
Pirro G |
PG |
|
Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom. |
| de Jong MA |
|
de Jong |
Markus A |
MA |
|
Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands. |
| Zhu G |
|
Zhu |
Gu |
G |
|
QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
| Adhikari K |
|
Adhikari |
Kaustubh |
K |
|
Department of Genetics, Evolution, and Environment, University College London, London, United Kingdom. |
| Li D |
|
Li |
Dan |
D |
|
Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS), Shanghai, China. |
| Li Y |
|
Li |
Yi |
Y |
|
CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, University of Chinese Academy of Sciences (CAS), Beijing, China. |
| Pan B |
|
Pan |
Bo |
B |
|
Department of Auricular Reconstruction, Plastic Surgery Hospital, Beijing, China. |
| Feingold E |
|
Feingold |
Eleanor |
E |
|
Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, United States. |
| Marazita ML |
|
Marazita |
Mary L |
ML |
|
Department of Human Genetics, University of Pittsburgh, Pittsburgh, United States. |
| Shaffer JR |
|
Shaffer |
John R |
JR |
|
Department of Human Genetics, University of Pittsburgh, Pittsburgh, United States. |
| McAloney K |
|
McAloney |
Kerrie |
K |
|
QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
| Xu SH |
|
Xu |
Shu-Hua |
SH |
|
Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China. |
| Jin L |
|
Jin |
Li |
L |
|
Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China. |
| Wang S |
|
Wang |
Sijia |
S |
|
Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China. |
| de Vrij FM |
|
de Vrij |
Femke Ms |
FM |
|
Department of Psychiatry, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands. |
| Lendemeijer B |
|
Lendemeijer |
Bas |
B |
|
Department of Psychiatry, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands. |
| Richmond S |
|
Richmond |
Stephen |
S |
|
Applied Clinical Research and Public Health, University Dental School, Cardiff University, Cardiff, United Kingdom. |
| Zhurov A |
|
Zhurov |
Alexei |
A |
|
Applied Clinical Research and Public Health, University Dental School, Cardiff University, Cardiff, United Kingdom. |
| Lewis S |
|
Lewis |
Sarah |
S |
|
Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, United Kingdom. |
| Sharp GC |
|
Sharp |
Gemma C |
GC |
|
School of Oral and Dental Sciences, University of Bristol, Bristol, United Kingdom. |
| Paternoster L |
|
Paternoster |
Lavinia |
L |
|
Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, United Kingdom. |
| Thompson H |
|
Thompson |
Holly |
H |
|
Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, United Kingdom. |
| Gonzalez-Jose R |
|
Gonzalez-Jose |
Rolando |
R |
|
Instituto Patagonico de Ciencias Sociales y Humanas, CENPAT-CONICET, Puerto Madryn, Argentina. |
| Bortolini MC |
|
Bortolini |
Maria Catira |
MC |
|
Departamento de Genetica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. |
| Canizales-Quinteros S |
|
Canizales-Quinteros |
Samuel |
S |
|
UNAM-Instituto Nacional de Medicina Genomica, Facultad de Quımica, Unidad de Genomica de Poblaciones Aplicada a la Salud, Mexico City, Mexico. |
| Gallo C |
|
Gallo |
Carla |
C |
|
Laboratorios de Investigacion y Desarrollo, Facultad de Ciencias y Filosofıa, Universidad Peruana Cayetano Heredia, Lima, Peru. |
| Poletti G |
|
Poletti |
Giovanni |
G |
|
Laboratorios de Investigacion y Desarrollo, Facultad de Ciencias y Filosofıa, Universidad Peruana Cayetano Heredia, Lima, Peru. |
| Bedoya G |
|
Bedoya |
Gabriel |
G |
|
GENMOL (Genetica Molecular), Universidad de Antioquia, Medellın, Colombia. |
| Rothhammer F |
|
Rothhammer |
Francisco |
F |
|
Instituto de Alta Investigacion, Universidad de Tarapaca, Arica, Chile. |
| Uitterlinden AG |
|
Uitterlinden |
André G |
AG |
|
Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands. |
| Ikram MA |
|
Ikram |
M Arfan |
MA |
|
Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands. |
| Wolvius E |
|
Wolvius |
Eppo |
E |
|
Department of Oral & Maxillofacial Surgery, Special Dental Care, and Orthodontics, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands. |
| Kushner SA |
|
Kushner |
Steven A |
SA |
|
Department of Psychiatry, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands. |
| Nijsten TE |
|
Nijsten |
Tamar Ec |
TE |
|
Department of Dermatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands. |
| Palstra RT |
|
Palstra |
Robert-Jan Ts |
RT |
|
Department of Biochemistry, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands. |
| Boehringer S |
|
Boehringer |
Stefan |
S |
|
Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands. |
| Medland SE |
|
Medland |
Sarah E |
SE |
|
QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
| Tang K |
|
Tang |
Kun |
K |
|
Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS), Shanghai, China. |
| Ruiz-Linares A |
|
Ruiz-Linares |
Andres |
A |
|
Aix-Marseille Université, CNRS, EFS, ADES, Marseille, France. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
| Spector TD |
|
Spector |
Timothy D |
TD |
|
Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom. |
| Stergiakouli E |
|
Stergiakouli |
Evie |
E |
|
School of Oral and Dental Sciences, University of Bristol, Bristol, United Kingdom. |
| Weinberg SM |
|
Weinberg |
Seth M |
SM |
|
Department of Anthropology, University of Pittsburgh, Pittsburgh, United States. |
| Liu F |
|
Liu |
Fan |
F |
|
CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, University of Chinese Academy of Sciences (CAS), Beijing, China. |
| Kayser M |
|
Kayser |
Manfred |
M |
|
Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands. |
|
International Visible Trait Genetics (VisiGen) Consortium |
|
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| INVESTIGATORS |
|
| LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
| On Behalf Of The International Visible Trait Genetics VisiGen Consortium |
|
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|
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| JOURNAL |
|
| VOLUME: 8 |
| ISSUE: |
| TITLE: eLife |
| ISOABBREVIATION: Elife |
| YEAR: 2019 |
| MONTH: 11 |
| DAY: 26 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 2050-084X |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Elife |
| COUNTRY: England |
| ISSNLINKING: 2050-084X |
| NLMUNIQUEID: 101579614 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Meta-Analysis |
| Research Support, N.I.H., Extramural |
| Research Support, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
|
|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| 31271338 |
National Natural Science Foundation of China |
International |
| R01 DE027023 |
NIDCR NIH HHS |
United States |
| APP103119 |
National Health and Medical Research Council |
International |
| 2017YFC0803501-Z04 |
National Key Research and Development Program China |
International |
| R01-DE027023 |
NIDCR NIH HHS |
United States |
| PhD Fellowship |
China Scholarship Council |
International |
| 102215/2/13/2 |
Medical Research Council |
United Kingdom |
| U01-DE020078 |
NIDCR NIH HHS |
United States |
| 31711530221 |
National Natural Science Foundation of China |
International |
| F/07 134/DF |
Leverhulme Trust |
International |
| 2015FY111700 |
National Basic Research Program of China |
International |
| 31771388 |
National Natural Science Foundation of China |
International |
| 911-03-012 |
Netherlands Organisation for Scientific Research |
International |
| 91731303 |
National Natural Science Foundation of China |
International |
| 31711530331 |
National Natural Science Foundation of China |
International |
| APP1103623 |
Australian NHMRC Fellowship |
International |
| 16JC1400504 |
Science and Technology Commission of Shanghai Municipality |
International |
| 2017YFC083501 |
National Key R&D Program of China |
International |
| U01 DE020078 |
NIDCR NIH HHS |
United States |
| 91651507 |
National Science Foundation of China |
International |
| 2016YFC0906403 |
National Key Research and Development Program China |
International |
| National Key R&D Program of China (2017YFC083501) |
Ministry of Science and Technology of the People's Republic of China |
International |
| 30890034 |
National Natural Science Foundation of China |
International |
| 050-060-810 |
Netherlands Organisation for Scientific Research |
International |
| R01-DE016148 |
NIDCR NIH HHS |
United States |
| 911-03-012 |
Netherlands Organization of Scientific Research |
International |
| U01-DE20078 |
NIDCR NIH HHS |
United States |
| 315014 |
National Natural Science Foundation of China |
International |
| 1750102005011 |
Netherlands Organisation for Scientific Research |
International |
| CPT-1602, Estrategia para sostenibilidad 2016-2018 grupo GENMOL |
Universidad de Antioquia |
International |
| 175.010.2005.011 |
Netherlands Organisation for Scientific Research |
International |
| 050-060-810 |
Netherlands Genomics Initiative |
International |
| R01 DE016148 |
NIDCR NIH HHS |
United States |
| MC_PC_15018 |
Medical Research Council |
United Kingdom |
| 740580 (VISAGE) |
Horizon 2020 - Research and Innovation Framework Programme |
International |
| XDC010400100 |
Strategic Priority Reserach Program Chinese Academy of Sciences |
International |
| Major Project 2017SHZDZX01 |
Shanghai Municipal Science and Technology Commission |
International |
| Strategic Priority Research Program (XDC010400100) |
Chinese Academy of Sciences |
International |
| 1750102005011 |
Netherlands Organization of Scientific Research |
International |
| X01-HG007821 |
NIDCR NIH HHS |
United States |
| F/07 134/DF |
Levelhulm Trust |
International |
| QYZDJ-SSW-SYS009 |
Chinese Academy of Sciences |
International |
| MC_UU_00011/1 |
Medical Research Council |
United Kingdom |
| Fellowship (APP1103623) |
National Health and Medical Research Council |
International |
| BB/I021213/1 |
BBSRC |
International |
| G9815508 |
Medical Research Council |
United Kingdom |
| 91631307 |
National Natural Science Foundation of China |
International |
| 740580 (VISAGE) |
European Union Horizon 2020 Research and Innovation Programme |
International |
|
| GENERAL NOTE |
|
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| KEYWORDS |
|
| KEYWORD |
| European |
| GWAS |
| face |
| gene regulation |
| genetics |
| genome-wide association study |
| genomics |
| human |
| images |
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| MESH HEADINGS |
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| DESCRIPTORNAME |
QUALIFIERNAME |
| Adolescent |
|
| Adult |
|
| Anatomic Landmarks |
|
| Body Patterning |
genetics |
| Child |
genetics |
| Child, Preschool |
genetics |
| Face |
anatomy & histology |
| Female |
anatomy & histology |
| Gene Expression Regulation, Developmental |
genetics |
| Gene Ontology |
genetics |
| Genetic Loci |
genetics |
| Genetic Variation |
genetics |
| Genome-Wide Association Study |
genetics |
| Genotype |
genetics |
| Humans |
genetics |
| Imaging, Three-Dimensional |
genetics |
| Male |
genetics |
| Maxillofacial Development |
genetics |
| Middle Aged |
genetics |
| Multifactorial Inheritance |
genetics |
| Phenotype |
genetics |
| Polymorphism, Single Nucleotide |
genetics |
| Young Adult |
genetics |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
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| CHEMICALS |
|
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| OTHER ID's |
|
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|
