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Insights into the genetic architecture of the human face
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Abstract
The human face is complex and multipartite, and characterization of its genetic architecture remains challenging. Using a multivariate genome-wide association study meta-analysis of 8,246 European individuals, we identified 203 genome-wide-significant signals (120 also study-wide significant) associated with normal-range facial variation. Follow-up analyses indicate that the regions surrounding these signals are enriched for enhancer activity in cranial neural crest cells and craniofacial tissues, several regions harbor multiple signals with associations to different facial phenotypes, and there is evidence for potential coordinated actions of variants. In summary, our analyses provide insights into the understanding of how complex morphological traits are shaped by both individual and coordinated genetic actions.
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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 [30]
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Metadata
- Authors
- White, J. D., Indencleef, K., Naqvi, S., Eller, R. J., Hoskens, H., Roosenboom, J., Lee, M. K., Li, J., Mohammed, J., Richmond, S., Quillen, E. E., Norton, H. L., Feingold, E., Swigut, T., Marazita, M. L., Peeters, H., Hens, G., Shaffer, J. R., Wysocka, J., Walsh, S., Weinberg, S. M., Shriver, M. D., & Claes, P.
- Affiliations
- Pennsylvania State University (US)
- Universitair Ziekenhuis Leuven (BE)
- Stanford Medicine (US)
- Indiana University – Purdue University Indianapolis (US)
- University of Pittsburgh (US)
- Cardiff University (GB)
- Wake Forest University Health Sciences (US)
- University of Cincinnati (US)
- KU Leuven (BE)
- Howard Hughes Medical Institute (US)
- Corresponding author
- White, Julie D.
- Indencleef, Karlijne
- Claes, Peter
- ORCID
- White, Julie D.
- Indencleef, Karlijne
- Naqvi, Sahin
- Eller, Ryan J.
- Hoskens, Hanne
- Roosenboom, Jasmien
- Lee, Myoung Keun
- Li, Jiarui
- Mohammed, Jaaved
- Richmond, Stephen
- Quillen, Ellen E.
- Norton, Heather L.
- Feingold, Eleanor
- Swigut, Tomek
- Marazita, Mary L.
- Peeters, Hilde
- Hens, Greet
- Shaffer, John R.
- Wysocka, Joanna
- Walsh, Susan
- Weinberg, Seth M.
- Shriver, Mark D.
- Claes, Peter
- Venue
- Nature Genetics
- Published
- 2020-12-07
- Volume
- 53
- Issue
- 1
- Pages
- 45-53
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC7796995
- OpenAlex
- W3113354915
- Cited by
- 166
- References
- 115
- Citations by year
- 2026: 22 · 2025: 29 · 2024: 30 · 2023: 27 · 2022: 32 · 2021: 24 · 2020: 2
- FWCI
- 12.46
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature Genetics (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Lirias (submittedVersion, other-oa)
- Funders
- U.S. Department of Defense
- Howard Hughes Medical Institute
- March of Dimes Foundation (1-FY15-312)
- University of Pennsylvania
- University of Washington
- University of Cincinnati
- Indiana University-Purdue University Indianapolis
- Pennsylvania State University
- Wellcome Trust (102215/2/13/2), 217065/Z/19/Z)
- University of California Research Initiatives
- University of Bristol (102215/2/13/2)
- Fonds Wetenschappelijk Onderzoek (G078518N)
- KU Leuven (C14/15/081, C14/20/081, BOF‐C1)
- Vlaamse regering (G078518N)
- National Institutes of Health (X01-HG007485, HHSN268201200008I, HG007485, 102215/2/13/2)
- University of Illinois at Urbana-Champaign
- Medical Research Council (102215, ref: 102215/2/13/2, 102215/2/13/2, MC_PC_15018, MC_PC_19009)
- National Heart, Lung, and Blood Institute (HHSN268201200008I, HHSN268201200008C)
- National Human Genome Research Institute (X01‐HG007485, X01‐HG007821)
- National Institute of Dental and Craniofacial Research (DE-016148, #HHSN268201200008I, R01DE027023, R01DE016148, U01DE020078, U01DE024430, DE027023, X01-HG007821, U01-DE020078, R01-DE016148, and R01-DE027023)
- National Institute of Justice (-R2-CX-, 2008-DN-BX-K125, 2015-R2-CX-0023, 2014-DN-BX-K031, 2018-DU-BX-0219)
- 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
- human face, facial morphology, genetic architecture, facial variation, cranial neural crest cells, enhancer activity, gene-gene interaction, European populations
- MeSH terms
- Acetylation, Enhancer Elements, Genetic, Epistasis, Genetic, Extremities, Face, United Kingdom, Histones, Humans, Lysine, Neural Crest, Phenotype, Skull, United States, Meta-Analysis as Topic, Multivariate Analysis, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Genetic Loci
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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