Genome-wide meta-analysis of cognitive empathy: Heritability, and correlates with sex, neuropsychiatric conditions and cognition

V. Warrier*, K. L. Grasby, F. Uzefovsky, R. Toro, P. Smith, B. Chakrabarti, J. Khadake, E. Mawbey-Adamson, N. Litterman, J. J. Hottenga, G. Lubke, D. I. Boomsma, N. G. Martin, P. K. Hatemi, S. E. Medland, D. A. Hinds, T. Bourgeron, S. Baron-Cohen

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

We conducted a genome-wide meta-analysis of cognitive empathy using the 'Reading the Mind in the Eyes' Test (Eyes Test) in 88,056 research volunteers of European Ancestry (44,574 females and 43,482 males) from 23andMe Inc., and an additional 1497 research volunteers of European Ancestry (891 females and 606 males) from the Brisbane Longitudinal Twin Study. We confirmed a female advantage on the Eyes Test (Cohen's d=0.21, P<2.2 × 10 -16), and identified a locus in 3p26.1 that is associated with scores on the Eyes Test in females (rs7641347, P meta =1.58 × 10 -8). Common single nucleotide polymorphisms explained 5.8% (95% CI: 4.5%-7.2%; P=1.00 × 10 -17) of the total trait variance in both sexes, and we identified a twin heritability of 28% (95% CI: 13%-42%). Finally, we identified significant genetic correlation between the Eyes Test and anorexia nervosa, openness (NEO-Five Factor Inventory), and different measures of educational attainment and cognitive aptitude.

Original languageEnglish
Pages (from-to)1402-1409
Number of pages8
JournalMolecular Psychiatry
Volume23
Issue number6
DOIs
Publication statusPublished - 6 Jun 2018

Funding

This study was funded by grants from the Templeton World Charity Foundation, Inc., the Medical Research Council, the Wellcome Trust, the Autism Research Trust, the Institut Pasteur, the CNRS and the University Paris Diderot. V.W. is funded by St John's College, Cambridge, and Cambridge Commonwealth Trust. The research was carried out in association with the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care East of England at Cambridgeshire and Peterborough NHS Foundation Trust. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The research was supported by the National Human Genome Research Institute of the National Institutes of Health (grant number R44HG006981). The National Science Foundation (grant numbers 0729493 and 0721707) supported the research on the Brisbane Longitudinal Twin Study. F.U. was supported by the British Friends of Haifa University, the Israel Science Foundation (grant no. 449/14), the British Friends of Hebrew University and the Joseph Levy Charitable Foundation. T.B. was supported by the Institut Pasteur, the University Paris Diderot, CNRS, and the Bettencourt-Schueller Foundation. We acknowledge with gratitude the generous support of Drs Dennis and Mireille Gillings in strengthening the collaboration between SBC and TB, and between Cambridge University and the Institut Pasteur. This publication was made possible through the support of a grant from the Templeton World Charity Foundation, Inc. The opinions expressed in this publication are those of the authors, and do not necessarily reflect the views of Templeton World Charity Foundation, Inc. We thank the research participants and employees of 23andMe for making this work possible. We also thank the volunteers of the Brisbane Longitudinal Twin Study and the NIHR Cambridge BioResource. Finally, we thank Silviu-Alin Bacanu, Hilary Finucane, Brendan Bulik-Sullivan, Carrie Allison, Michael Lombardo and Richard Bethlehem for helpful discussions. 1402 1409 10.1038/mp.2017.122 EN V Warrier Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridgeshire, UK K L Grasby QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia F Uzefovsky Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridgeshire, UK Department of Psychology, Ben Gurion University of the Negev, Be’er Sheva, Israel R Toro CNRS UMR 3571: Genes, Synapses and Cognition, Institut Pasteur, Paris, France Université Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France Institut Pasteur, Paris, France http://orcid.org/0000-0002-6671-858X P Smith Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridgeshire, UK B Chakrabarti Centre for Integrative Neuroscience and Neurodynamics, School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK http://orcid.org/0000-0002-6649-7895 J Khadake NIHR Cambridge BioResource, Cambridge University and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK E Mawbey-Adamson NIHR Cambridge BioResource, Cambridge University and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK N Litterman 23andMe Inc., Mountain View, CA, USA J-J Hottenga Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands EMGO+ Institute for Health and Care Research, VU Medical Center, Amsterdam, The Netherlands Neuroscience Campus Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands G Lubke Department of Psychology, University of Notre Dame, South Bend, IN, USA D I Boomsma Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands N G Martin QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia P K Hatemi Political Science, Microbiology and Biochemistry, Pennsylvania State University, University Park, PA, USA S E Medland QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia D A Hinds 23andMe Inc., Mountain View, CA, USA T Bourgeron CNRS UMR 3571: Genes, Synapses and Cognition, Institut Pasteur, Paris, France Université Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France Institut Pasteur, Paris, France S Baron-Cohen Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridgeshire, UK CLASS Clinic, Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), Cambridgeshire, UK mp2017122 10.1038/mp.2017.122 2016 11 19 2017 4 8 2017 4 12 2017 06 06 We conducted a genome-wide meta-analysis of cognitive empathy using the ‘Reading the Mind in the Eyes’ Test (Eyes Test) in 88,056 research volunteers of European Ancestry (44,574 females and 43,482 males) from 23andMe Inc., and an additional 1497 research volunteers of European Ancestry (891 females and 606 males) from the Brisbane Longitudinal Twin Study. We confirmed a female advantage on the Eyes Test (Cohen’s d=0.21, P<2.2 × 10 −16 ), and identified a locus in 3p26.1 that is associated with scores on the Eyes Test in females (rs7641347, P meta =1.58 × 10 −8 ). Common single nucleotide polymorphisms explained 5.8% (95% CI: 4.5%–7.2%; P=1.00 × 10 −17 ) of the total trait variance in both sexes, and we identified a twin heritability of 28% (95% CI: 13%–42%). Finally, we identified significant genetic correlation between the Eyes Test and anorexia nervosa, openness (NEO-Five Factor Inventory), and different measures of educational attainment and cognitive aptitude.

FundersFunder number
23andMe Inc
National Human Genome Research InstituteR44HG006981
University of Notre Dame
Central Manchester University Hospitals NHS Foundation Trust
Pennsylvania State University
Heart of England NHS Foundation Trust606
Medical Research Council
National Institute for Health Research
University of Cambridge
University of Reading
Vrije Universiteit Amsterdam
Institut Pasteur
Ben-Gurion University of the Negev

    Keywords

    • Journal Article

    Cohort Studies

    • Netherlands Twin Register (NTR)

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