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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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Journal Article
Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents
2015
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
