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Genome-wide mapping of global-to-local genetic effects on human facial shape
Open accessAbstract
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.
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“A significant portion of the 16 ear-related loci discussed here have been shown to have strong ties to human facial structure [8,15,21,22,30].”
From Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci (2023) · cites this paper as [22]
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Metadata
- Authors
- Claes, P., Roosenboom, J., White, J. D., Swigut, T., Sero, D., Li, J., Lee, M. K., Zaidi, A., Mattern, B. C., Liebowitz, C., Pearson, L., González, T., Leslie, E. J., Carlson, J. C., Orlova, E., Suetens, P., Vandermeulen, D., Feingold, E., Marazita, M. L., Shaffer, J. R., Wysocka, J., Shriver, M. D., & Weinberg, S. M.
- Affiliations
- Universitair Ziekenhuis Leuven (BE)
- University of Pittsburgh (US)
- Pennsylvania State University (US)
- Stanford Medicine (US)
- Corresponding author
- Claes, Peter
- Wysocka, Joanna
- Shriver, Mark D.
- Weinberg, Seth M.
- ORCID
- Claes, Peter
- Roosenboom, Jasmien
- White, Julie D.
- Swigut, Tomek
- Sero, Dzemila
- Lee, Myoung Keun
- Zaidi, Arslan
- Mattern, Brooke C.
- Pearson, Laurel
- 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.
- Venue
- Nature Genetics
- Published
- 2018-02-19
- Volume
- 50
- Issue
- 3
- Pages
- 414-423
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC5937280
- OpenAlex
- W2789017128
- Semantic Scholar
- c3fa862579fa588c95e4d3f5a5445fc1c2531c54
- Cited by
- 235
- References
- 62
- Citations by year
- 2026: 21 · 2025: 24 · 2024: 17 · 2023: 31 · 2022: 24 · 2021: 44 · 2020: 29 · 2019: 30 · 2018: 14
- FWCI
- 17.94
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Lirias (KU Leuven) (submittedVersion)
- Funders
- KU Leuven
- National Institute of Dental and Craniofacial Research (R01DE027023, R01DE016148, U01DE020078, K99DE025060, R00DE025060, U01DE024430, U01DE020057)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Morphological variations and asymmetry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- facial shape, facial morphology, genetic loci, cranial neural crest cells, pleiotropy, morphological characters, European ancestry
- MeSH terms
- Adult, Chromosome Mapping, Face, Genotype, Humans, Maxillofacial Development, Phenotype, United States, Cohort Studies, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Quantitative Trait Loci, White People, Genome-Wide Association Study, Young Adult, Genetic Association Studies
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