Genome-wide mapping of global-to-local genetic effects on human facial shape

Genome-wide association scans of complex multipartite traits like the human face typically use preselected phenotypic measures. Here we report a data-driven approach to phenotyping facial shape at multiple levels of organization, allowing for an open-ended description of facial variation while prese...

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Published inNature genetics Vol. 50; no. 3; pp. 414 - 423
Main Authors Claes, Peter, Roosenboom, Jasmien, White, Julie D., Swigut, Tomek, Sero, Dzemila, Li, Jiarui, Lee, Myoung Keun, Zaidi, Arslan, Mattern, Brooke C., Liebowitz, Corey, Pearson, Laurel, González, Tomás, Leslie, Elizabeth J., Carlson, Jenna C., Orlova, Ekaterina, Suetens, Paul, Vandermeulen, Dirk, Feingold, Eleanor, Marazita, Mary L., Shaffer, John R., Wysocka, Joanna, Shriver, Mark D., Weinberg, Seth M.
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group US 01.03.2018
Nature Publishing Group
Subjects
45/43
631/208
631/208/205
631/208/457
Adult
Age
Agriculture
Animal Genetics and Genomics
Binding sites
Biomedical and Life Sciences
Biomedicine
Cancer Research
Chromatin
Chromosome Mapping
Cohort Studies
Face - anatomy & histology
Gene Function
Gene loci
Gene mapping
Genealogy
Genetic Association Studies
Genetic effects
Genetics
Genome-Wide Association Study
Genomes
Genotype
Genotype & phenotype
Human Genetics
Humans
Mapping
Maxillofacial Development - genetics
Multifactorial Inheritance - genetics
Neural crest
Phenotype
Phenotyping
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Shape effects
Studies
United States
White People - genetics
Young Adult
United States
United States > US
Online AccessGet full text
ISSN1061-4036
1546-1718
1546-1718
DOI10.1038/s41588-018-0057-4

Cover

Abstract Genome-wide association scans of complex multipartite traits like the human face typically use preselected phenotypic measures. Here we report a data-driven approach to phenotyping facial shape at multiple levels of organization, allowing for an open-ended description of facial variation while preserving statistical power. In a sample of 2,329 persons of European ancestry, we identified 38 loci, 15 of which replicated in an independent European sample ( n  = 1,719). Four loci were completely new. For the others, additional support ( n  = 9) or pleiotropic effects ( n  = 2) were found in the literature, but the results reported here were further refined. All 15 replicated loci highlighted distinctive patterns of global-to-local genetic effects on facial shape and showed enrichment for active chromatin elements in human cranial neural crest cells, suggesting an early developmental origin of the facial variation captured. These results have implications for studies of facial genetics and other complex morphological traits. The authors report a data-driven approach to phenotyping 3D facial shape. They apply their methodology to 2,329 individuals of European ancestry and identify 38 loci that associate with specific facial morphologies, some of which overlap with neural-crest-specific regulatory regions.
AbstractList Genome-wide association scans of complex multipartite traits like the human face typically use preselected phenotypic measures. Here we report a data-driven approach to phenotyping facial shape at multiple levels of organization, allowing for an open-ended description of facial variation, while preserving statistical power. In a sample of 2,329 persons of European ancestry we identified 38 loci, 15 of which replicated in an independent European sample (n=1,719). Four loci were completely novel. For the others, additional support (n=9) or pleiotropic effects (n=2) were found in the literature, but the results reported here were further refined. All 15 replicated loci revealed distinctive patterns of global-to-local genetic effects on facial shape and showed enrichment for active chromatin elements in human cranial neural crest cells, suggesting an early developmental origin of the facial variation captured. These results have implications for studies of facial genetics and other complex morphological traits.
Genome-wide association scans of complex multipartite traits like the human face typically use preselected phenotypic measures. Here we report a data-driven approach to phenotyping facial shape at multiple levels of organization, allowing for an open-ended description of facial variation while preserving statistical power. In a sample of 2,329 persons of European ancestry, we identified 38 loci, 15 of which replicated in an independent European sample (n = 1,719). Four loci were completely new. For the others, additional support (n = 9) or pleiotropic effects (n = 2) were found in the literature, but the results reported here were further refined. All 15 replicated loci highlighted distinctive patterns of global-to-local genetic effects on facial shape and showed enrichment for active chromatin elements in human cranial neural crest cells, suggesting an early developmental origin of the facial variation captured. These results have implications for studies of facial genetics and other complex morphological traits.
Genome-wide association scans of complex multipartite traits like the human face typically use preselected phenotypic measures. Here we report a data-driven approach to phenotyping facial shape at multiple levels of organization, allowing for an open-ended description of facial variation while preserving statistical power. In a sample of 2,329 persons of European ancestry, we identified 38 loci, 15 of which replicated in an independent European sample (n = 1,719). Four loci were completely new. For the others, additional support (n = 9) or pleiotropic effects (n = 2) were found in the literature, but the results reported here were further refined. All 15 replicated loci highlighted distinctive patterns of global-to-local genetic effects on facial shape and showed enrichment for active chromatin elements in human cranial neural crest cells, suggesting an early developmental origin of the facial variation captured. These results have implications for studies of facial genetics and other complex morphological traits.Genome-wide association scans of complex multipartite traits like the human face typically use preselected phenotypic measures. Here we report a data-driven approach to phenotyping facial shape at multiple levels of organization, allowing for an open-ended description of facial variation while preserving statistical power. In a sample of 2,329 persons of European ancestry, we identified 38 loci, 15 of which replicated in an independent European sample (n = 1,719). Four loci were completely new. For the others, additional support (n = 9) or pleiotropic effects (n = 2) were found in the literature, but the results reported here were further refined. All 15 replicated loci highlighted distinctive patterns of global-to-local genetic effects on facial shape and showed enrichment for active chromatin elements in human cranial neural crest cells, suggesting an early developmental origin of the facial variation captured. These results have implications for studies of facial genetics and other complex morphological traits.
Genome-wide association scans of complex multipartite traits like the human face typically use preselected phenotypic measures. Here we report a data-driven approach to phenotyping facial shape at multiple levels of organization, allowing for an open-ended description of facial variation while preserving statistical power. In a sample of 2,329 persons of European ancestry, we identified 38 loci, 15 of which replicated in an independent European sample ( n  = 1,719). Four loci were completely new. For the others, additional support ( n  = 9) or pleiotropic effects ( n  = 2) were found in the literature, but the results reported here were further refined. All 15 replicated loci highlighted distinctive patterns of global-to-local genetic effects on facial shape and showed enrichment for active chromatin elements in human cranial neural crest cells, suggesting an early developmental origin of the facial variation captured. These results have implications for studies of facial genetics and other complex morphological traits. The authors report a data-driven approach to phenotyping 3D facial shape. They apply their methodology to 2,329 individuals of European ancestry and identify 38 loci that associate with specific facial morphologies, some of which overlap with neural-crest-specific regulatory regions.
Author Orlova, Ekaterina
Carlson, Jenna C.
Li, Jiarui
Zaidi, Arslan
Feingold, Eleanor
Mattern, Brooke C.
Claes, Peter
White, Julie D.
Shaffer, John R.
Suetens, Paul
Lee, Myoung Keun
Pearson, Laurel
Wysocka, Joanna
Leslie, Elizabeth J.
Weinberg, Seth M.
Liebowitz, Corey
Shriver, Mark D.
Roosenboom, Jasmien
Swigut, Tomek
González, Tomás
Vandermeulen, Dirk
Sero, Dzemila
Marazita, Mary L.
AuthorAffiliation 10 Department of Anthropology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
5 Department of Anthropology, Penn State University, University Park, Pennsylvania, United States of America
7 Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
2 Medical Imaging Research Center, MIRC, UZ Leuven, Leuven, Belgium
1 Department of Electrical Engineering, ESAT/PSI, KU Leuven, Leuven, Belgium
9 Department of Developmental Biology, Stanford University School of Medicine, Stanford, California, United States of America
4 Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
3 Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
6 Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California, United States of America
8 Department of Human Genetics, University of Pittsburgh,
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– name: 8 Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
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– name: 5 Department of Anthropology, Penn State University, University Park, Pennsylvania, United States of America
– name: 10 Department of Anthropology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/29459680$$D View this record in MEDLINE/PubMed
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Snippet Genome-wide association scans of complex multipartite traits like the human face typically use preselected phenotypic measures. Here we report a data-driven...
SourceID pubmedcentral
proquest
pubmed
crossref
springer
SourceType Open Access Repository
Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 414
SubjectTerms 45/43
631/208
631/208/205
631/208/457
Adult
Age
Agriculture
Animal Genetics and Genomics
Binding sites
Biomedical and Life Sciences
Biomedicine
Cancer Research
Chromatin
Chromosome Mapping
Cohort Studies
Face - anatomy & histology
Gene Function
Gene loci
Gene mapping
Genealogy
Genetic Association Studies
Genetic effects
Genetics
Genome-Wide Association Study
Genomes
Genotype
Genotype & phenotype
Human Genetics
Humans
Mapping
Maxillofacial Development - genetics
Multifactorial Inheritance - genetics
Neural crest
Phenotype
Phenotyping
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Shape effects
Studies
United States
White People - genetics
Young Adult
Title Genome-wide mapping of global-to-local genetic effects on human facial shape
URI https://link.springer.com/article/10.1038/s41588-018-0057-4
https://www.ncbi.nlm.nih.gov/pubmed/29459680
https://www.proquest.com/docview/2197773768
https://www.proquest.com/docview/2007114735
https://pubmed.ncbi.nlm.nih.gov/PMC5937280
Volume 50
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