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; L Medina; A Kepa; A Fernandes; B Ruggeri; F. Carvalho; G Cocks; T. Banaschewski; G Barker; A Bokde; C Büchel; P Conrod; H Flor; A. Heinz; J Gallinat; H Garavan; P Gowland; R Brühl; C Lawrence; K. Mann; M Martinot; F Nees; M. Lathrop; J-B Poline; M Rietschel; P Thompson; M Fauth-Bühler; M Smolka; Z Pausova; T Paus; J Feng; G. Schumann

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 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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Journal articles

Domain :

Life Sciences [q-bio]

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

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

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