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

S Desrivières 1, * A Lourdusamy 1 C. Tao 2 R Toro 3 T Jia 1 E Loth 1 L Medina 1 A Kepa 1 A Fernandes 1 B Ruggeri 1 F. Carvalho 1 G Cocks 1 T. Banaschewski 4, 5 G Barker 1 A Bokde 6 C Büchel 7 P Conrod 1, 8, 9 H Flor 10, 11 A. Heinz 12 J Gallinat 12 H Garavan 6, 13 P Gowland 13 R Brühl 14 C Lawrence 15 K. Mann 4 M Martinot 16, 17 F Nees 4 M. Lathrop 18 J-B Poline 19 M Rietschel 4 P Thompson 20 M Fauth-Bühler 4 M Smolka 21 Z Pausova 22 T Paus 15, 22, 23 J Feng 2, 24 G. Schumann 1
* Corresponding author
1 Institute of Psychiatry, Psychology & Neuroscience, King's College London
2 Fudan University [Shanghai]
3 GHFC (UMR_3571 / U-Pasteur_1) - Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions
4 Central Institute of Mental Health [Mannheim]
5 University of Heidelberg, Medical Faculty
6 Trinity College Dublin
7 UKE - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
8 CHU Sainte Justine [Montréal]
9 Université de Montréal [Montréal]
10 Medical Faculty [Mannheim]
11 Universität Heidelberg [Heidelberg]
12 Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin
13 University of Vermont [Burlington]
14 PTB - Physikalisch-Technische Bundesanstalt [Berlin]
15 UON - University of Nottingham, UK
16 U1000 - Neuroimagerie en psychiatrie
17 Maison de Solenn [CHU Cochin]
18 CNG - Centre National de Génotypage
19 NEUROSPIN - Service NEUROSPIN
20 School of Medicine [Los Angeles]
21 TUD - Technische Universität Dresden
22 University of Toronto
23 McGill University
24 University of Warwick [Coventry]
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.
Keywords : intelligence cortical thickness neural stem cell neuroimaging lateralization adolescent
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S Desrivières, A Lourdusamy, C. Tao, R Toro, T Jia, et al.. Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents. Molecular Psychiatry, Nature Publishing Group, 2015, 20 (2), pp.263-274. ⟨10.1038/mp.2013.197⟩. ⟨pasteur-01967174⟩

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