Gene Variant May Affect Intellectual Ability in Adolescents

It is time to return to specificity to address a recent study that was brought to my attention a few days ago.

4 days ago a study was released entitled "Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents." The study was conducted by Desrivières and a team of 36 other researches along with the IMAGEN Consortium, published in the Journal of Molecular Psychiatry.

The researchers conducted a large-scale association study in 1,583 adolescents to identify genes which affected cortical thickness. They identified the rs7171755 polymorphism, which acted in cis (oriented on the same side hemisphere) to the expression of the NPTN gene. The results suggest that there is a potential role for regional synaptic dysfunctions in forms of intellectual deficits.

NPTN expression from GeneCards.

Going beyond the abstract, the data was obtained from a sample of 1,583 healthy adolescents, all age 14, obtained from the IMAGEN project -- a project which endorses the study of association between genetics and neural function. Each adolescent was given a verbal and nonverbal IQ score using the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) and SNP genotyping was extracted from whole blood samples. The association between the identified SNP and cortical thickness, verbal IQ and nonverbal IQ were identified using linear regression analyses. Data on NPTN expression was collected from both mice and human brain samples.

The results showed that for the left hemisphere of the brain, the rs7171755 polymorphism on chromosome 15 passed the threshold for significance in affecting cortical thickness; however on the right hemisphere of the brain, while the largest association was found on chromosome 11, none passed the significance threshold, and neither handedness (prior led by the widely-known right/left brain phenomenon) nor ethnicity affected these results. On the left hemisphere, the number of minor alleles at rs7171755 was inversely correlated with mean cortical thickness. The correlation between mean cortical thickness and nonverbal IQ for the left hemisphere was 0.074, and 0.041 for the right hemisphere; also, there was a positive correlation (r = 0.033) between left cortical thickness and school performance. There were no statistically significant correlations between verbal IQ and cortical thickness.

These results suggest that rs7171755 may have a statistically significant influence on nonverbal IQ by affecting cortical thickness. The researchers tested this through mediation analyses and found that the minor A-allele at rs7171755 associated with lower nonverbal IQ scores (β = −1.239); the association was mediated by significant indirect effects on the SNP for nonverbal IQ (β = −0.1851) while direct effects were not significant. There was also a correlation between rs7171755 and verbal IQ scores (β = −1.5048), partially as a result of indirect effects on the SNP on left pars orbitalis thickness, the rest from other factors.

The overall implications of this study suggest that localized effects of rs7171755 on the RPTN gene in brain structure can explain a small amount of the variation in IQ scores (estimate at around 0.5% of the total variation), and this association is found mostly with nonverbal IQ, which leaves the door open for early intervention of adolescent education which would be more conducive to literacy. At the same time, the authors acknowledge the age specificity and low effect size of the study. While normally I am skeptical of such findings, the results of this study suggest to me a realistic potential for association between the rs7171755 polymorphism and IQ scores. It still remains, however, that I am skeptical of the usefulness of IQ scores in measuring intelligence.

In the end, despite some of its shortcomings and the small explanation it suggests, this should be taken as a decent pilot study for further testing of this gene and the associated risk alleles found to be of significance in this study; yet scientists and researchers alike should note that although there is a high heritability estimate for cortical thickness (as noted in the study), it is also greatly susceptible to environmental influences.

Thank you very much for reading.



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Reference:

Desrivières et al. (2014). Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents. Molecular Psychiatry DOI: 10.1038/mp.2013.197