Abstract

Human brain anatomy is strikingly diverse and highly inheritable: genetic factors may explain up to 80% of its variability. Prior studies have tried to detect genetic variants with a large effect on neuroanatomical diversity, but those currently identified account for <5% of the variance. Here, based on our analyses of neuroimaging and whole-genome genotyping data from 1765 subjects, we show that up to 54% of this heritability is captured by large numbers of single-nucleotide polymorphisms of small-effect spread throughout the genome, especially within genes and close regulatory regions. The genetic bases of neuroanatomical diversity appear to be relatively independent of those of body size (height), but shared with those of verbal intelligence scores. The study of this genomic architecture should help us better understand brain evolution and disease.

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Acknowledgements

This work was supported by the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement-related behaviour in normal brain function and psychopathology; LSHM-CT-2007-037286), the FP7 projects ADAMS (Genomic variations underlying common neuropsychiatric diseases and diseases related to cognitive traits in different human populations; 242257), the Innovative Medicine Initiative Project EU-AIMS (115300-2), the Medical Research Council Programme Grant ‘Developmental pathways into adolescent substance abuse’ (93558), the Swedish Funding Agency FORMAS, the German Bundesministerium und Forschung (FKZ: 01EV0711), Institut Pasteur, CNRS, Université Paris Diderot, the Bettencourt-Schueller Foundation, the Conny-Maeva Foundation, the Orange Foundation, the FondaMental Foundation and the Cognacq-Jay Foundation.

Author information

Author notes

    • T Bourgeron

    Shared last authorship.

Affiliations

  1. Human Genetics and Cognitive Functions, Neuroscience Department, Institut Pasteur, Paris, France

    • R Toro
    • , G Huguet
    •  & T Bourgeron
  2. CNRS URA 2182 ‘Genes, synapses and cognition’, Paris, France

    • R Toro
    • , G Huguet
    •  & T Bourgeron
  3. Université Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France

    • R Toro
    • , G Huguet
    •  & T Bourgeron
  4. Henry H. Wheeler, Jr. Brain Imaging Center, University of California at Berkeley, Berkeley, CA, USA

    • J-B Poline
    •  & V Frouin
  5. Neurospin, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Paris, France

    • J-B Poline
  6. Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, King’s College London, London, UK

    • E Loth
    • , G J Barker
    • , F M Carvalho
    • , P Conrod
    •  & G Schumann
  7. MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK

    • E Loth
    • , F M Carvalho
    •  & G Schumann
  8. Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    • T Banaschewski
  9. Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neurosciences, Trinity College Dublin, Dublin, Ireland

    • A Bokde
    •  & H Garavan
  10. University Medical Centre Hamburg-Eppendorf, Hamburg, Germany

    • C Büchel
  11. Department of Psychiatry, Université de Montreal, CHU Ste Justine Hospital, Montreal, QC, Canada

    • P Conrod
  12. Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    • M Fauth-Bühler
    •  & K Mann
  13. Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    • H Flor
    •  & F Nees
  14. Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité–Universitätsmedizin Berlin, Berlin, Germany

    • J Gallinat
    • , A Heinz
    •  & A Ströhle
  15. Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA

    • H Garavan
    •  & P Gowland
  16. Physikalisch-Technische Bundesanstalt, Berlin, Germany

    • B Ittermann
  17. School of Psychology, University of Nottingham, Nottingham, UK

    • C Lawrence
    •  & T Paus
  18. Institut National de la Santé et de la Recherche Medicale, INSERM CEA Unit 1000, 'Imaging & Psychiatry', University Paris Sud, Orsay, France

    • H Lemaître
  19. Department of Adolescent Psychopathology and Medicine, Assistance Publique Hôpitaux de Paris, Maison de Solenn, Université Paris Descartes, Paris, France

    • H Lemaître
  20. Psychology and Psychiatry Department, Rotman Research Institute, University of Toronto, Toronto, ON, Canada

    • T Paus
  21. Department of Psychiatry, Université de Montreal, CHU Ste Justine Hospital, Montreal, QC, Canada

    • T Paus
  22. The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    • Z Pausova
  23. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    • M Rietschel
  24. Department of Psychology and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK

    • T Robbins
  25. Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany

    • M N Smolka
  26. Department of Psychology, Neuroimaging Center, Technische Universität Dresden, Dresden, Germany

    • M N Smolka
  27. Fondamental Foundation, Créteil, France

    • G Schumann
    •  & T Bourgeron

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Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to R Toro.

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DOI

https://doi.org/10.1038/mp.2014.99

Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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