期刊
MOLECULAR PSYCHIATRY
卷 20, 期 2, 页码 263-274出版社
SPRINGERNATURE
DOI: 10.1038/mp.2013.197
关键词
adolescent; cortical thickness; intelligence; lateralization; neural stem cell; neuroimaging
资金
- European Union [LSHM-CT- 2007-037286]
- German Ministry of Education and Research (BMBF) [01EV0711]
- FP7 project IMAGEMEND (Development of effective imaging tools for diagnosis, monitoring and management of mental disorders)
- Innovative Medicine Initiative Project EU-AIMS [115300-2]
- Medical Research Council Programme Grant 'Developmental pathways into adolescent substance abuse' [G93558]
- Swedish Research Council (FORMAS)
- United Kingdom National Institute for Health Research (NIHR) Biomedical Research Centre Mental Health
- MRC [G0901858] Funding Source: UKRI
- Medical Research Council [G0901858, G9817803B] Funding Source: researchfish
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 x 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.
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