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

S Desrivières; A Lourdusamy; C Tao; R Toro; T Jia; E Loth; Lourdes Martinez Medina; A Kepa; A Fernandes; B Ruggeri; Fabiana Mesquita De Carvalho; G Cocks; T Banaschewski; G J Barker; A L W Bokde; C Büchel; P J Conrod; H Flor; A Heinz; J Gallinat; H Garavan; P Gowland; R Brühl; C Lawrence; K Mann; M L P Martinot; F Nees; M Lathrop; J-B Poline; M Rietschel; P Thompson; M Fauth-Bühler; M N Smolka; Z Pausova; T Paus; J Feng; G Schumann; The IMAGEN Consortium

doi:10.1038/mp.2013.197

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

S Desrivières
, A Lourdusamy
, C Tao
, R Toro
, T Jia
, E Loth
, Lourdes Martinez Medina
, A Kepa
, A Fernandes
, B Ruggeri
, Fabiana Mesquita De Carvalho
, G Cocks
, T Banaschewski
, G J Barker
, A L W Bokde
, C Büchel
, P J Conrod
, H Flor
, A Heinz
, J Gallinat

H Garavan, P Gowland, R Brühl, C Lawrence, K Mann, M L P Martinot, F Nees, M Lathrop, J-B Poline, M Rietschel, P Thompson, M Fauth-Bühler, M N Smolka, Z Pausova, T Paus, J Feng, G Schumann, The IMAGEN Consortium

Fudan University
1] Human Genetics and Cognitive Functions, Institut Pasteur, Paris, France [2] CNRS URA 2182, Genes, synapses and cognition, Institut Pasteur, Paris, France.
Heidelberg University
Trinity College Dublin
Department of Systems Neuroscience, Universitaetsklinikum Hamburg Eppendorf, Hamburg, Germany.
Charité University of Medicine Berlin
1] Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland [2] Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA.
Univ Vermont, Burlington
Physikalisch-Technische Bundesanstalt
University of Nottingham
Central Institute of Mental Health Mannheim
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.
Centre National de Génotypage, Evry, France.
UVSQ Versailles Saint-Quentin-en-Yvelines University
University of California, Los Angeles
TU Dresden
The Hospital for Sick Children Research Institute
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.
1] Center for Computational Systems Biology, Fudan University, Shanghai, China [2] Department of Computer Science and Centre for Scientific Computing, Warwick University, Coventry, UK.

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Pages (from-to)	263-274
Number of pages	12
Journal	Molecular Psychiatry
Volume	20
Issue number	2
Early online date	11 Feb 2014
DOIs	https://doi.org/10.1038/mp.2013.197
Publication status	Published - 1 Feb 2015

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Single nucleotide polymorphism in the neuroplastin locus_SCHUMANN_Publishedonline11February2014_GOLD VoR (CC BY NC ND)Final published version, 2.35 MBLicence: CC BY-NC-ND

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Desrivières, S., Lourdusamy, A., Tao, C., Toro, R., Jia, T., Loth, E., Martinez Medina, L., Kepa, A., Fernandes, A., Ruggeri, B., Mesquita De Carvalho, F., Cocks, G., Banaschewski, T., Barker, G. J., Bokde, A. L. W., Büchel, C., Conrod, P. J., Flor, H., Heinz, A., ... The IMAGEN Consortium (2015). Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents. Molecular Psychiatry, 20(2), 263-274. https://doi.org/10.1038/mp.2013.197

@article{0d8d9d9f0adf4ae6a59af23fe24ada48,

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.",

author = "S Desrivi{\`e}res and A Lourdusamy and C Tao and R Toro and T Jia and E Loth and \{Martinez Medina\}, Lourdes and A Kepa and A Fernandes and B Ruggeri and \{Mesquita De Carvalho\}, Fabiana and G Cocks and T Banaschewski and Barker, \{G J\} and Bokde, \{A L W\} and C B{\"u}chel and Conrod, \{P J\} and H Flor and A Heinz and J Gallinat and H Garavan and P Gowland and R Br{\"u}hl and C Lawrence and K Mann and Martinot, \{M L P\} and F Nees and M Lathrop and J-B Poline and M Rietschel and P Thompson and M Fauth-B{\"u}hler and Smolka, \{M N\} and Z Pausova and T Paus and J Feng and G Schumann and \{The IMAGEN Consortium\}",

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doi = "10.1038/mp.2013.197",

language = "English",

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pages = "263--274",

journal = "Molecular Psychiatry",

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Desrivières, S , Lourdusamy, A, Tao, C, Toro, R, Jia, T , Loth, E , Martinez Medina, L , Kepa, A , Fernandes, A , Ruggeri, B , Mesquita De Carvalho, F , Cocks, G, Banaschewski, T, Barker, GJ, Bokde, ALW, Büchel, C, Conrod, PJ, Flor, H, Heinz, A, Gallinat, J, Garavan, H, Gowland, P, Brühl, R, Lawrence, C, Mann, K, Martinot, MLP, Nees, F, Lathrop, M, Poline, J-B, Rietschel, M, Thompson, P, Fauth-Bühler, M, Smolka, MN, Pausova, Z, Paus, T, Feng, J, Schumann, G & The IMAGEN Consortium 2015, 'Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents', Molecular Psychiatry, vol. 20, no. 2, pp. 263-274. https://doi.org/10.1038/mp.2013.197

TY - JOUR

T1 - Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents

AU - Desrivières, S

AU - Lourdusamy, A

AU - Tao, C

AU - Toro, R

AU - Jia, T

AU - Loth, E

AU - Martinez Medina, Lourdes

AU - Kepa, A

AU - Fernandes, A

AU - Ruggeri, B

AU - Mesquita De Carvalho, Fabiana

AU - Cocks, G

AU - Banaschewski, T

AU - Barker, G J

AU - Bokde, A L W

AU - Büchel, C

AU - Conrod, P J

AU - Flor, H

AU - Heinz, A

AU - Gallinat, J

AU - Garavan, H

AU - Gowland, P

AU - Brühl, R

AU - Lawrence, C

AU - Mann, K

AU - Martinot, M L P

AU - Nees, F

AU - Lathrop, M

AU - Poline, J-B

AU - Rietschel, M

AU - Thompson, P

AU - Fauth-Bühler, M

AU - Smolka, M N

AU - Pausova, Z

AU - Paus, T

AU - Feng, J

AU - Schumann, G

AU - The IMAGEN Consortium

PY - 2015/2/1

Y1 - 2015/2/1

N2 - 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.

AB - 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.

U2 - 10.1038/mp.2013.197

DO - 10.1038/mp.2013.197

M3 - Article

C2 - 24514566

SN - 1359-4184

VL - 20

SP - 263

EP - 274

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 2

ER -

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

Abstract

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