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Mol Psychiatry. 2015 Feb;20(2):263-74. doi: 10.1038/mp.2013.197. Epub 2014 Feb 11.

Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents.

Author information

1
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.
2
Center for Computational Systems Biology, Fudan University, Shanghai, China.
3
1] Human Genetics and Cognitive Functions, Institut Pasteur, Paris, France [2] CNRS URA 2182, Genes, synapses and cognition, Institut Pasteur, Paris, France.
4
Institute of Psychiatry, King's College, London, UK.
5
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.
6
Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
7
Department of Systems Neuroscience, Universitaetsklinikum Hamburg Eppendorf, Hamburg, Germany.
8
1] Institute of Psychiatry, King's College, London, UK [2] Department of Psychiatry, Université de Montreal, CHU Ste Justine Hospital, Montreal, QC, Canada.
9
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
10
Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin, Berlin, Germany.
11
1] Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland [2] Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA.
12
Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA.
13
Physikalisch-Technische Bundesanstalt (PTB), Braunschweig und Berlin, Berlin, Germany.
14
School of Psychology, University of Nottingham, Nottingham, UK.
15
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany.
16
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.
17
Centre National de Génotypage, Evry, France.
18
Neurospin, Commissariat àl'Energie Atomique et aux Energies Alternatives, Paris, France.
19
Imaging Genetics Center/Laborarory of Neuro Imaging, UCLA School of Medicine, Los Angeles, CA, USA.
20
Department of Addictive Behaviour and Addiction Medicine, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany.
21
1] Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany [2] Department of Psychology, Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
22
The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
23
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.
24
1] Center for Computational Systems Biology, Fudan University, Shanghai, China [2] Department of Computer Science and Centre for Scientific Computing, Warwick University, Coventry, UK.

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.

PMID:
24514566
PMCID:
PMC4051592
DOI:
10.1038/mp.2013.197
[Indexed for MEDLINE]
Free PMC Article

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