eLife (Nov 2019)
Novel genetic loci affecting facial shape variation in humans
- Ziyi Xiong,
- Gabriela Dankova,
- Laurence J Howe,
- Myoung Keun Lee,
- Pirro G Hysi,
- Markus A de Jong,
- Gu Zhu,
- Kaustubh Adhikari,
- Dan Li,
- Yi Li,
- Bo Pan,
- Eleanor Feingold,
- Mary L Marazita,
- John R Shaffer,
- Kerrie McAloney,
- Shu-Hua Xu,
- Li Jin,
- Sijia Wang,
- Femke MS de Vrij,
- Bas Lendemeijer,
- Stephen Richmond,
- Alexei Zhurov,
- Sarah Lewis,
- Gemma C Sharp,
- Lavinia Paternoster,
- Holly Thompson,
- Rolando Gonzalez-Jose,
- Maria Catira Bortolini,
- Samuel Canizales-Quinteros,
- Carla Gallo,
- Giovanni Poletti,
- Gabriel Bedoya,
- Francisco Rothhammer,
- André G Uitterlinden,
- M Arfan Ikram,
- Eppo Wolvius,
- Steven A Kushner,
- Tamar EC Nijsten,
- Robert-Jan TS Palstra,
- Stefan Boehringer,
- Sarah E Medland,
- Kun Tang,
- Andres Ruiz-Linares,
- Nicholas G Martin,
- Timothy D Spector,
- Evie Stergiakouli,
- Seth M Weinberg,
- Fan Liu,
- Manfred Kayser,
- On behalf of the International Visible Trait Genetics (VisiGen) Consortium
Affiliations
- Ziyi Xiong
- Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands; Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, University of Chinese Academy of Sciences (CAS), Beijing, China
- Gabriela Dankova
- Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands
- Laurence J Howe
- Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, United Kingdom
- Myoung Keun Lee
- Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, United States
- Pirro G Hysi
- Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom
- Markus A de Jong
- Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands; Department of Oral & Maxillofacial Surgery, Special Dental Care, and Orthodontics, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands; Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
- Gu Zhu
- QIMR Berghofer Medical Research Institute, Brisbane, Australia
- Kaustubh Adhikari
- ORCiD
- Department of Genetics, Evolution, and Environment, University College London, London, United Kingdom
- Dan Li
- CAS Key Laboratory of Computational Biology, Chinese Academy of Sciences (CAS), Shanghai, China; CAS-MPG Partner Institute for Computational Biology (PICB), Chinese Academy of Sciences (CAS), Shanghai, China; Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS), Shanghai, China
- Yi Li
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, University of Chinese Academy of Sciences (CAS), Beijing, China
- Bo Pan
- Department of Auricular Reconstruction, Plastic Surgery Hospital, Beijing, China
- Eleanor Feingold
- Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, United States
- Mary L Marazita
- ORCiD
- Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, United States; Department of Human Genetics, University of Pittsburgh, Pittsburgh, United States
- John R Shaffer
- ORCiD
- Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, United States; Department of Human Genetics, University of Pittsburgh, Pittsburgh, United States
- Kerrie McAloney
- QIMR Berghofer Medical Research Institute, Brisbane, Australia
- Shu-Hua Xu
- CAS Key Laboratory of Computational Biology, Chinese Academy of Sciences (CAS), Shanghai, China; CAS-MPG Partner Institute for Computational Biology (PICB), Chinese Academy of Sciences (CAS), Shanghai, China; Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS), Shanghai, China; School of Life Science and Technology, ShanghaiTech University, Shanghai, China; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China
- Li Jin
- CAS Key Laboratory of Computational Biology, Chinese Academy of Sciences (CAS), Shanghai, China; CAS-MPG Partner Institute for Computational Biology (PICB), Chinese Academy of Sciences (CAS), Shanghai, China; Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS), Shanghai, China; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China; Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China
- Sijia Wang
- CAS Key Laboratory of Computational Biology, Chinese Academy of Sciences (CAS), Shanghai, China; CAS-MPG Partner Institute for Computational Biology (PICB), Chinese Academy of Sciences (CAS), Shanghai, China; Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS), Shanghai, China; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China
- Femke MS de Vrij
- ORCiD
- Department of Psychiatry, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands
- Bas Lendemeijer
- Department of Psychiatry, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands
- Stephen Richmond
- Applied Clinical Research and Public Health, University Dental School, Cardiff University, Cardiff, United Kingdom
- Alexei Zhurov
- Applied Clinical Research and Public Health, University Dental School, Cardiff University, Cardiff, United Kingdom
- Sarah Lewis
- Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, United Kingdom
- Gemma C Sharp
- ORCiD
- Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, United Kingdom; School of Oral and Dental Sciences, University of Bristol, Bristol, United Kingdom
- Lavinia Paternoster
- Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, United Kingdom
- Holly Thompson
- Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, United Kingdom
- Rolando Gonzalez-Jose
- Instituto Patagonico de Ciencias Sociales y Humanas, CENPAT-CONICET, Puerto Madryn, Argentina
- Maria Catira Bortolini
- Departamento de Genetica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
- Samuel Canizales-Quinteros
- UNAM-Instituto Nacional de Medicina Genomica, Facultad de Quımica, Unidad de Genomica de Poblaciones Aplicada a la Salud, Mexico City, Mexico
- Carla Gallo
- ORCiD
- Laboratorios de Investigacion y Desarrollo, Facultad de Ciencias y Filosofıa, Universidad Peruana Cayetano Heredia, Lima, Peru
- Giovanni Poletti
- Laboratorios de Investigacion y Desarrollo, Facultad de Ciencias y Filosofıa, Universidad Peruana Cayetano Heredia, Lima, Peru
- Gabriel Bedoya
- GENMOL (Genetica Molecular), Universidad de Antioquia, Medellın, Colombia
- Francisco Rothhammer
- Instituto de Alta Investigacion, Universidad de Tarapaca, Arica, Chile
- André G Uitterlinden
- Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands; Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands
- M Arfan Ikram
- Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands
- Eppo Wolvius
- Department of Oral & Maxillofacial Surgery, Special Dental Care, and Orthodontics, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands
- Steven A Kushner
- ORCiD
- Department of Psychiatry, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands
- Tamar EC Nijsten
- Department of Dermatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands
- Robert-Jan TS Palstra
- Department of Biochemistry, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands
- Stefan Boehringer
- ORCiD
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
- Sarah E Medland
- QIMR Berghofer Medical Research Institute, Brisbane, Australia
- Kun Tang
- CAS Key Laboratory of Computational Biology, Chinese Academy of Sciences (CAS), Shanghai, China; CAS-MPG Partner Institute for Computational Biology (PICB), Chinese Academy of Sciences (CAS), Shanghai, China; Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS), Shanghai, China
- Andres Ruiz-Linares
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China; Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China; Aix-Marseille Université, CNRS, EFS, ADES, Marseille, France
- Nicholas G Martin
- QIMR Berghofer Medical Research Institute, Brisbane, Australia
- Timothy D Spector
- Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom
- Evie Stergiakouli
- Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, United Kingdom; School of Oral and Dental Sciences, University of Bristol, Bristol, United Kingdom
- Seth M Weinberg
- Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, United States; Department of Human Genetics, University of Pittsburgh, Pittsburgh, United States; Department of Anthropology, University of Pittsburgh, Pittsburgh, United States
- Fan Liu
- Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, University of Chinese Academy of Sciences (CAS), Beijing, China
- Manfred Kayser
- ORCiD
- Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands
- On behalf of the International Visible Trait Genetics (VisiGen) Consortium
- DOI
- https://doi.org/10.7554/eLife.49898
- Journal volume & issue
-
Vol. 8
Abstract
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 × 10−8), 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 × 10−3). 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 cis-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.
Keywords
