title: Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents.
abstract: Despite the recognition that cortical thickness is heritable and correlates with intellectual ability in children and adolescents, the genes contributing to individual differences in these traits remain unknown. We conducted a large-scale association study in 1583 adolescents to identify genes affecting cortical thickness. Single-nucleotide polymorphisms (SNPs; n=54,837) within genes whose expression changed between stages of growth and differentiation of a human neural stem cell line were selected for association analyses with average cortical thickness. We identified a variant, rs7171755, associating with thinner cortex in the left hemisphere (P=1.12 × 10(-)(7)), particularly in the frontal and temporal lobes. Localized effects of this SNP on cortical thickness differently affected verbal and nonverbal intellectual abilities. The rs7171755 polymorphism acted in cis to affect expression in the human brain of the synaptic cell adhesion glycoprotein-encoding gene NPTN. We also found that cortical thickness and NPTN expression were on average higher in the right hemisphere, suggesting that asymmetric NPTN expression may render the left hemisphere more sensitive to the effects of NPTN mutations, accounting for the lateralized effect of rs7171755 found in our study. Altogether, our findings support a potential role for regional synaptic dysfunctions in forms of intellectual deficits.
authors: 1] Institute of Psychiatry, King's College, London, UK [2] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors: S
authors: S
authors: Desrivières
authors: 1] Institute of Psychiatry, King's College, London, UK [2] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors: A
authors: A
authors: Lourdusamy
authors: Center for Computational Systems Biology, Fudan University, Shanghai, China.
authors: C
authors: C
authors: Tao
authors: 1] Human Genetics and Cognitive Functions, Institut Pasteur, Paris, France [2] CNRS URA 2182, Genes, synapses and cognition, Institut Pasteur, Paris, France.
authors: R
authors: R
authors: Toro
authors: 1] Institute of Psychiatry, King's College, London, UK [2] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors: T
authors: T
authors: Jia
authors: 1] Institute of Psychiatry, King's College, London, UK [2] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors: E
authors: E
authors: Loth
authors: 1] Institute of Psychiatry, King's College, London, UK [2] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors: L M
authors: LM
authors: Medina
authors: 1] Institute of Psychiatry, King's College, London, UK [2] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors: A
authors: A
authors: Kepa
authors: 1] Institute of Psychiatry, King's College, London, UK [2] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors: A
authors: A
authors: Fernandes
authors: 1] Institute of Psychiatry, King's College, London, UK [2] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors: B
authors: B
authors: Ruggeri
authors: 1] Institute of Psychiatry, King's College, London, UK [2] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors: F M
authors: FM
authors: Carvalho
authors: Institute of Psychiatry, King's College, London, UK.
authors: G
authors: G
authors: Cocks
authors: 1] Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany [2] Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors: T
authors: T
authors: Banaschewski
authors: Institute of Psychiatry, King's College, London, UK.
authors: G J
authors: 0000000252147421
authors: GJ
authors: Barker
authors: Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors: A L W
authors: AL
authors: Bokde
authors: Department of Systems Neuroscience, Universitaetsklinikum Hamburg Eppendorf, Hamburg, Germany.
authors: C
authors: C
authors: Büchel
authors: 1] Institute of Psychiatry, King's College, London, UK [2] Department of Psychiatry, Université de Montreal, CHU Ste Justine Hospital, Montreal, QC, Canada.
authors: P J
authors: PJ
authors: Conrod
authors: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: H
authors: H
authors: Flor
authors: Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin, Berlin, Germany.
authors: A
authors: A
authors: Heinz
authors: Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin, Berlin, Germany.
authors: J
authors: J
authors: Gallinat
authors: 1] Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland [2] Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA.
authors: H
authors: H
authors: Garavan
authors: Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA.
authors: P
authors: P
authors: Gowland
authors: Physikalisch-Technische Bundesanstalt (PTB), Braunschweig und Berlin, Berlin, Germany.
authors: R
authors: R
authors: Brühl
authors: School of Psychology, University of Nottingham, Nottingham, UK.
authors: C
authors: C
authors: Lawrence
authors: Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany.
authors: K
authors: K
authors: Mann
authors: 1] Institut National de la Santé et de la Recherche Médicale, INSERM CEA Unit 1000 'Imaging & Psychiatry', University Paris Sud, Orsay, France [2] AP-HP Department of Adolescent Psychopathology and Medicine, Maison de Solenn, University Paris Descartes, Paris, France.
authors: M L P
authors: ML
authors: Martinot
authors: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: F
authors: F
authors: Nees
authors: Centre National de Génotypage, Evry, France.
authors: M
authors: M
authors: Lathrop
authors: Neurospin, Commissariat àl'Energie Atomique et aux Energies Alternatives, Paris, France.
authors: J-B
authors: JB
authors: Poline
authors: Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany.
authors: M
authors: M
authors: Rietschel
authors: Imaging Genetics Center/Laborarory of Neuro Imaging, UCLA School of Medicine, Los Angeles, CA, USA.
authors: P
authors: P
authors: Thompson
authors: Department of Addictive Behaviour and Addiction Medicine, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany.
authors: M
authors: M
authors: Fauth-Bühler
authors: 1] Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany [2] Department of Psychology, Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
authors: M N
authors: MN
authors: Smolka
authors: The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors: Z
authors: Z
authors: Pausova
authors: 1] School of Psychology, University of Nottingham, Nottingham, UK [2] Rotman Research Institute, University of Toronto, Toronto, ON, Canada [3] Montreal Neurological Institute, McGill University, Montreal, Canada.
authors: T
authors: T
authors: Paus
authors: 1] Center for Computational Systems Biology, Fudan University, Shanghai, China [2] Department of Computer Science and Centre for Scientific Computing, Warwick University, Coventry, UK.
authors: J
authors: J
authors: Feng
authors: 1] Institute of Psychiatry, King's College, London, UK [2] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors: G
authors: G
authors: Schumann
mesh_terms: D000293:Adolescent; D000818:Animals; D001921:Brain / Q000033:anatomy & histology*; D002478:Cells, Cultured; D003071:Cognition / Q000502:physiology*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007360:Intelligence / Q000502:physiology*; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D015201:Meta-Analysis as Topic; D051379:Mice; D008822:Mice, Transgenic; D046228:Microarray Analysis; D058953:Neural Stem Cells / Q000502:physiology; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D008562:Membrane Glycoproteins; C518360:NPTN protein, human