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

Desrivi�res, S; the IMAGEN Consortium; Lourdusamy, A; Tao, C; Toro, R; Jia, T; Loth, E; Medina, L M; Kepa, A; Fernandes, A; Ruggeri, B; Carvalho, F M; Cocks, G; Banaschewski, T; Barker, G J; Bokde, A L W; B�chel, C; Conrod, P J; Flor, H; Heinz, A; Gallinat, J; Garavan, H; Gowland, P; Br�hl, R; Lawrence, C; Mann, K; Martinot, M L P; Nees, F; Lathrop, M; Poline, J-B; Rietschel, M; Thompson, P; Fauth-B�hler, M; Smolka, M N; Pausova, Z; Paus, T; Feng, J; Schumann, G

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.

Citation

Desrivières, S., the IMAGEN Consortium, Lourdusamy, A., Tao, C., Toro, R., Jia, T., Loth, E., Medina, L. M., Kepa, A., Fernandes, A., Ruggeri, B., Carvalho, F. M., Cocks, G., Banaschewski, T., Barker, G. J., Bokde, A. L. W., Büchel, C., Conrod, P. J., Flor, H., Heinz, A., …Schumann, G. (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

• Journal Article Type: Article
• Acceptance Date: Dec 9, 2013
• Online Publication Date: Feb 11, 2014
• Publication Date: 2015-02
• Deposit Date: Mar 17, 2020
• Publicly Available Date: Mar 17, 2020
• Journal: Molecular Psychiatry
• Print ISSN: 1359-4184
• Electronic ISSN: 1476-5578
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 20
• Issue: 2
• Pages: 263-274
• DOI: https://doi.org/10.1038/mp.2013.197
• Keywords: Molecular Biology; Cellular and Molecular Neuroscience; Psychiatry and Mental health
• Public URL: https://nottingham-repository.worktribe.com/output/4159911
• Publisher URL: https://www.nature.com/articles/mp2013197#citeas
• Additional Information: Desrivières, S., Lourdusamy, A., Tao, C. et al. Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents. Mol Psychiatry 20, 263–274 (2015). https://doi.org/10.1038/mp.2013.197