Genomic architecture of human neuroanatomical diversity

R Toro; J-B Poline; G Huguet; E Loth; V Frouin; T Banaschewski; G J Barker; A Bokde; C Büchel; F M Carvalho; P Conrod; M Fauth-Bühler; H Flor; J Gallinat; H Garavan; P Gowland; A Heinz; B Ittermann; C Lawrence; H Lemaître; K Mann; F Nees; T Paus; Z Pausova; M Rietschel; T Robbins; M N Smolka; A Ströhle; G Schumann; T Bourgeron; IMAGEN consortium

doi:10.1038/mp.2014.99

Genomic architecture of human neuroanatomical diversity

Mol Psychiatry. 2015 Aug;20(8):1011-6. doi: 10.1038/mp.2014.99. Epub 2014 Sep 16.

Authors

R Toro¹, J-B Poline², G Huguet¹, E Loth³, V Frouin⁴, T Banaschewski⁵, G J Barker⁶, A Bokde⁷, C Büchel⁸, F M Carvalho³, P Conrod⁹, M Fauth-Bühler¹⁰, H Flor¹¹, J Gallinat¹², H Garavan¹³, P Gowland¹⁴, A Heinz¹², B Ittermann¹⁵, C Lawrence¹⁶, H Lemaître¹⁷, K Mann¹⁰, F Nees¹¹, T Paus¹⁸, Z Pausova¹⁹, M Rietschel²⁰, T Robbins²¹, M N Smolka²², A Ströhle¹², G Schumann²³, T Bourgeron²⁴; IMAGEN consortium

Collaborators

IMAGEN consortium:
Gunter Schumann, Karl Mann, Trevor W Robbins, Arno Klaassen, Jean Baptiste Poline, Andreas Heinz, Patrick Constant, David N Stephens, Christian Büchel, Claudia Speiser, James Ireland, Anja Zysset, Tomas Paus, Dirk Lanzerath, Hugh Garavan, Jean-Luc Martinot, Bernd Ittermann, Michael Smolka, Zdenka Pausova

Affiliations

¹ 1] Human Genetics and Cognitive Functions, Neuroscience Department, Institut Pasteur, Paris, France [2] CNRS URA 2182 'Genes, synapses and cognition', Paris, France [3] Université Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France.
² 1] Henry H. Wheeler, Jr. Brain Imaging Center, University of California at Berkeley, Berkeley, CA, USA [2] Neurospin, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Paris, France.
³ 1] Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, King's College London, London, UK [2] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK.
⁴ Henry H. Wheeler, Jr. Brain Imaging Center, University of California at Berkeley, Berkeley, CA, USA.
⁵ Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁶ Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, King's College London, London, UK.
⁷ Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neurosciences, Trinity College Dublin, Dublin, Ireland.
⁸ University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
⁹ 1] Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, King's College London, London, UK [2] Department of Psychiatry, Université de Montreal, CHU Ste Justine Hospital, Montreal, QC, Canada.
¹⁰ Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
¹¹ Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
¹² Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹³ 1] Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neurosciences, Trinity College Dublin, Dublin, Ireland [2] Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA.
¹⁴ Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA.
¹⁵ Physikalisch-Technische Bundesanstalt, Berlin, Germany.
¹⁶ School of Psychology, University of Nottingham, Nottingham, UK.
¹⁷ 1] Institut National de la Santé et de la Recherche Medicale, INSERM CEA Unit 1000, 'Imaging & Psychiatry', University Paris Sud, Orsay, France [2] Department of Adolescent Psychopathology and Medicine, Assistance Publique Hôpitaux de Paris, Maison de Solenn, Université Paris Descartes, Paris, France.
¹⁸ 1] School of Psychology, University of Nottingham, Nottingham, UK [2] Psychology and Psychiatry Department, Rotman Research Institute, University of Toronto, Toronto, ON, Canada [3] Department of Psychiatry, Université de Montreal, CHU Ste Justine Hospital, Montreal, QC, Canada.
¹⁹ The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
²⁰ Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
²¹ Department of Psychology and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
²² 1] Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany [2] Department of Psychology, Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
²³ 1] Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, King's College London, London, UK [2] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK [3] Fondamental Foundation, Créteil, France.
²⁴ 1] Human Genetics and Cognitive Functions, Neuroscience Department, Institut Pasteur, Paris, France [2] CNRS URA 2182 'Genes, synapses and cognition', Paris, France [3] Université Paris Diderot, Sorbonne Paris Cité, Human Genetics and Cognitive Functions, Paris, France [4] Fondamental Foundation, Créteil, France.

PMID: 25224261
DOI: 10.1038/mp.2014.99

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.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Brain / anatomy & histology*
Cohort Studies
Computer Simulation
Female
Genome*
Genome-Wide Association Study
Genotyping Techniques
Humans
Magnetic Resonance Imaging
Male
Models, Genetic
Organ Size
Phenotype*
Polymorphism, Single Nucleotide

Abstract

Publication types

MeSH terms

Grants and funding