title: Global genetic variations predict brain response to faces.
abstract: Face expressions are a rich source of social signals. Here we estimated the proportion of phenotypic variance in the brain response to facial expressions explained by common genetic variance captured by ∼ 500,000 single nucleotide polymorphisms. Using genomic-relationship-matrix restricted maximum likelihood (GREML), we related this global genetic variance to that in the brain response to facial expressions, as assessed with functional magnetic resonance imaging (fMRI) in a community-based sample of adolescents (n = 1,620). Brain response to facial expressions was measured in 25 regions constituting a face network, as defined previously. In 9 out of these 25 regions, common genetic variance explained a significant proportion of phenotypic variance (40-50%) in their response to ambiguous facial expressions; this was not the case for angry facial expressions. Across the network, the strength of the genotype-phenotype relationship varied as a function of the inter-individual variability in the number of functional connections possessed by a given region (R(2) = 0.38, p<0.001). Furthermore, this variability showed an inverted U relationship with both the number of observed connections (R2 = 0.48, p<0.001) and the magnitude of brain response (R(2) = 0.32, p<0.001). Thus, a significant proportion of the brain response to facial expressions is predicted by common genetic variance in a subset of regions constituting the face network. These regions show the highest inter-individual variability in the number of connections with other network nodes, suggesting that the genetic model captures variations across the adolescent brains in co-opting these regions into the face network.
authors.affiliation: Rotman Research Institute, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Erin W
authors.initials: EW
authors.lastname: Dickie
authors.affiliation: Rotman Research Institute, University of Toronto, Toronto, Ontario, Canada; Philips Research North America, Briarcliff Manor, New York, United States of America.
authors.forename: Amir
authors.initials: A
authors.lastname: Tahmasebi
authors.affiliation: Rotman Research Institute, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Leon
authors.initials: L
authors.lastname: French
authors.affiliation: Rotman Research Institute, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Natasa
authors.initials: N
authors.lastname: Kovacevic
authors.affiliation: Central Institute of Mental Health, Mannheim, Germany; Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.affiliation: Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Barker
authors.affiliation: Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors.forename: Arun
authors.initials: A
authors.lastname: Bokde
authors.affiliation: Universitaetsklinikum Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Büchel
authors.affiliation: Institute of Psychiatry, King's College London, London, United Kingdom; Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital, Montreal, Quebec, Canada.
authors.forename: Patricia
authors.initials: P
authors.lastname: Conrod
authors.affiliation: Central Institute of Mental Health, Mannheim, Germany; Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Herta
authors.initials: H
authors.lastname: Flor
authors.affiliation: Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland; Departments of Psychiatry and Psychology, University of Vermont, Burlington, Vermont, United States of America.
authors.forename: Hugh
authors.initials: H
authors.lastname: Garavan
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Gallinat
authors.affiliation: Sir Peter Mansfield MR Centre, University of Nottingham, Nottingham, United Kindom.
authors.forename: Penny
authors.initials: P
authors.lastname: Gowland
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.affiliation: Physikalisch-Technische Bundesanstalt (PTB), Braunschweig und Berlin, Berlin, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Ittermann
authors.affiliation: School of Psychology, University of Nottingham, Nottingham, United Kindom.
authors.forename: Claire
authors.initials: C
authors.lastname: Lawrence
authors.affiliation: Central Institute of Mental Health, Mannheim, Germany; Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Mann
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, INSERM CEA Unit 1000 "Imaging & Psychiatry", University Paris Sud, Orsay, and AP-HP Department of Adolescent Psychopathology and Medicine, Maison de Solenn, University Paris Descartes, Paris, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Martinot
authors.affiliation: Central Institute of Mental Health, Mannheim, Germany; Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Nees
authors.affiliation: University of Warwick, Coventry, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nichols
authors.affiliation: Centre National de Génotypage, Evry, France.
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.affiliation: Institute of Psychiatry, King's College London, London, United Kingdom; MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, London, United Kingdom.
authors.forename: Eva
authors.initials: E
authors.lastname: Loth
authors.affiliation: The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Pausova
authors.affiliation: Central Institute of Mental Health, Mannheim, Germany; Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Marcela
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany; Neuroimaging Center, Department of Psychology, Technische Universität Dresden, Dresden, Germany.
authors.forename: Michal N
authors.initials: MN
authors.lastname: Smolka
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ströhle
authors.affiliation: Institute Pasteur, Paris, France.
authors.forename: Roberto
authors.initials: R
authors.lastname: Toro
authors.affiliation: Institute of Psychiatry, King's College London, London, United Kingdom; MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, London, United Kingdom.
authors.forename: Gunter
authors.initials: G
authors.lastname: Schumann
authors.affiliation: Rotman Research Institute, University of Toronto, Toronto, Ontario, Canada; School of Psychology, University of Nottingham, Nottingham, United Kindom.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Paus
mesh_terms: D000293:Adolescent; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D001931:Brain Mapping; D005149:Facial Expression; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*