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Research Article

Genetics of the human face: Identification of large-effect single gene variants

Daniel J. M. Crouch, Bruce Winney, Willem P. Koppen, William J. Christmas, Katarzyna Hutnik, Tammy Day, Devendra Meena, Abdelhamid Boumertit, Pirro Hysi, Ayrun Nessa, Tim D. Spector, Josef Kittler, and Walter F. Bodmer
  1. aCancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom;
  2. bDepartment of Oncology, University of Oxford, Oxford OX3 7DQ, United Kingdom;
  3. cCentre for Vision, Speech and Signal Processing, Department of Electronic Engineering, University of Surrey, Guildford GU2 7XH, United Kingdom;
  4. dTwinsUK, St. Thomas’ Hospital, King’s College London, London SE1 7EH, United Kingdom

See allHide authors and affiliations

PNAS January 23, 2018 115 (4) E676-E685; first published January 4, 2018; https://doi.org/10.1073/pnas.1708207114
Daniel J. M. Crouch
aCancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom;
bDepartment of Oncology, University of Oxford, Oxford OX3 7DQ, United Kingdom;
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Bruce Winney
aCancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom;
bDepartment of Oncology, University of Oxford, Oxford OX3 7DQ, United Kingdom;
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Willem P. Koppen
cCentre for Vision, Speech and Signal Processing, Department of Electronic Engineering, University of Surrey, Guildford GU2 7XH, United Kingdom;
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William J. Christmas
cCentre for Vision, Speech and Signal Processing, Department of Electronic Engineering, University of Surrey, Guildford GU2 7XH, United Kingdom;
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Katarzyna Hutnik
aCancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom;
bDepartment of Oncology, University of Oxford, Oxford OX3 7DQ, United Kingdom;
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Tammy Day
aCancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom;
bDepartment of Oncology, University of Oxford, Oxford OX3 7DQ, United Kingdom;
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Devendra Meena
aCancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom;
bDepartment of Oncology, University of Oxford, Oxford OX3 7DQ, United Kingdom;
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Abdelhamid Boumertit
aCancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom;
bDepartment of Oncology, University of Oxford, Oxford OX3 7DQ, United Kingdom;
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Pirro Hysi
dTwinsUK, St. Thomas’ Hospital, King’s College London, London SE1 7EH, United Kingdom
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Ayrun Nessa
dTwinsUK, St. Thomas’ Hospital, King’s College London, London SE1 7EH, United Kingdom
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Tim D. Spector
dTwinsUK, St. Thomas’ Hospital, King’s College London, London SE1 7EH, United Kingdom
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Josef Kittler
cCentre for Vision, Speech and Signal Processing, Department of Electronic Engineering, University of Surrey, Guildford GU2 7XH, United Kingdom;
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Walter F. Bodmer
aCancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom;
bDepartment of Oncology, University of Oxford, Oxford OX3 7DQ, United Kingdom;
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  • For correspondence: walter.bodmer@hertford.ox.ac.uk
  1. Contributed by Walter F. Bodmer, October 25, 2017 (sent for review May 18, 2017; reviewed by Marcus W. Feldman and Benjamin M. Neale)

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Significance

The human face is extraordinarily variable, and the extreme similarity of the faces of identical twins indicates that most of this variability is genetically determined. We have devised an approach to increase the chance of identifying specific large genetic effects on particular facial features, by choosing features with high heritability and selecting individuals with relatively extreme facial phenotypes for comparison with a control population. This has yielded three specific and replicated genetic variants, two for features of facial profiles, and one for the region around the eyes. Further application of these methods should enable the understanding, eventually at the molecular level, of the nature of this extraordinary genetic variability, which is such an important feature of our everyday human interactions.

Abstract

To discover specific variants with relatively large effects on the human face, we have devised an approach to identifying facial features with high heritability. This is based on using twin data to estimate the additive genetic value of each point on a face, as provided by a 3D camera system. In addition, we have used the ethnic difference between East Asian and European faces as a further source of face genetic variation. We use principal components (PCs) analysis to provide a fine definition of the surface features of human faces around the eyes and of the profile, and chose upper and lower 10% extremes of the most heritable PCs for looking for genetic associations. Using this strategy for the analysis of 3D images of 1,832 unique volunteers from the well-characterized People of the British Isles study and 1,567 unique twin images from the TwinsUK cohort, together with genetic data for 500,000 SNPs, we have identified three specific genetic variants with notable effects on facial profiles and eyes.

  • human genetics
  • facial features
  • SNPs
  • 3D imaging
  • additive genetic value

Footnotes

  • ↵1D.J.M.C. and B.W. contributed equally to this work.

  • ↵2Deceased May 12, 2017.

  • ↵3To whom correspondence should be addressed. Email: walter.bodmer{at}hertford.ox.ac.uk.
  • Author contributions: W.F.B. conceived the project; B.W. and T.D. organized collection of PoBI data; D.J.M.C., K.H., D.M., A.B., and W.F.B. assisted in data collection; P.H., A.N., and T.D.S. collected TwinsUK data; W.P.K. and W.J.C. conducted image registration analysis under supervision of J.K.; D.J.M.C. analyzed registered image data and genetic data under supervision of W.F.B.; D.J.M.C. and W.F.B. wrote the manuscript, with W.P.K. and W.J.C. contributing additional technical material; and B.W. and W.F.B. supervised the project.

  • Reviewers: M.W.F., Stanford University; and B.M.N., Broad Institute.

  • The authors declare no conflict of interest.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1708207114/-/DCSupplemental.

Published under the PNAS license.

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Genetics of the human face
Daniel J. M. Crouch, Bruce Winney, Willem P. Koppen, William J. Christmas, Katarzyna Hutnik, Tammy Day, Devendra Meena, Abdelhamid Boumertit, Pirro Hysi, Ayrun Nessa, Tim D. Spector, Josef Kittler, Walter F. Bodmer
Proceedings of the National Academy of Sciences Jan 2018, 115 (4) E676-E685; DOI: 10.1073/pnas.1708207114

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Genetics of the human face
Daniel J. M. Crouch, Bruce Winney, Willem P. Koppen, William J. Christmas, Katarzyna Hutnik, Tammy Day, Devendra Meena, Abdelhamid Boumertit, Pirro Hysi, Ayrun Nessa, Tim D. Spector, Josef Kittler, Walter F. Bodmer
Proceedings of the National Academy of Sciences Jan 2018, 115 (4) E676-E685; DOI: 10.1073/pnas.1708207114
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