Human cognitive ability is influenced by genetic variation in components of postsynaptic signalling complexes assembled by NMDA receptors and MAGUK proteins

Hill, W. D., Davies, G., Van De Lagemaat, L. N., Christoforou, A., Marioni, R. E., Fernandes, C. P. D., Liewald, D. C., Croning, M. D. R., Payton, A., Craig, L. C. A., Whalley, L. J., Horan, M., Ollier, W., Hansell, N. K., Wright, M. J., Martin, N. G., Montgomery, G. W., Steen, V. M., Le Hellard, S., Espeseth, T., Lundervold, A. J., Reinvang, I., Starr, J. M., Pendleton, N., Grant, S. G. N., Bates, T. C. and Deary, I. J. (2014) Human cognitive ability is influenced by genetic variation in components of postsynaptic signalling complexes assembled by NMDA receptors and MAGUK proteins. Translational Psychiatry, 4 1-8. doi:10.1038/tp.2013.114

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Author Hill, W. D.
Davies, G.
Van De Lagemaat, L. N.
Christoforou, A.
Marioni, R. E.
Fernandes, C. P. D.
Liewald, D. C.
Croning, M. D. R.
Payton, A.
Craig, L. C. A.
Whalley, L. J.
Horan, M.
Ollier, W.
Hansell, N. K.
Wright, M. J.
Martin, N. G.
Montgomery, G. W.
Steen, V. M.
Le Hellard, S.
Espeseth, T.
Lundervold, A. J.
Reinvang, I.
Starr, J. M.
Pendleton, N.
Grant, S. G. N.
Bates, T. C.
Deary, I. J.
Title Human cognitive ability is influenced by genetic variation in components of postsynaptic signalling complexes assembled by NMDA receptors and MAGUK proteins
Journal name Translational Psychiatry   Check publisher's open access policy
ISSN 2158-3188
Publication date 2014-01-07
Year available 2014
Sub-type Article (original research)
DOI 10.1038/tp.2013.114
Open Access Status DOI
Volume 4
Start page 1
End page 8
Total pages 8
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted abstract
Differences in general cognitive ability (intelligence) account for approximately half of the variation in any large battery of cognitive tests and are predictive of important life events including health. Genome-wide analyses of common single-nucleotide polymorphisms indicate that they jointly tag between a quarter and a half of the variance in intelligence. However, no single polymorphism has been reliably associated with variation in intelligence. It remains possible that these many small effects might be aggregated in networks of functionally linked genes. Here, we tested a network of 1461 genes in the postsynaptic density and associated complexes for an enriched association with intelligence. These were ascertained in 3511 individuals (the Cognitive Ageing Genetics in England and Scotland (CAGES) consortium) phenotyped for general cognitive ability, fluid cognitive ability, crystallised cognitive ability, memory and speed of processing. By analysing the results of a genome wide association study (GWAS) using Gene Set Enrichment Analysis, a significant enrichment was found for fluid cognitive ability for the proteins found in the complexes of N-methyl-D-aspartate receptor complex; P = 0.002. Replication was sought in two additional cohorts (N = 670 and 2062). A meta-analytic P-value of 0.003 was found when these were combined with the CAGES consortium. The results suggest that genetic variation in the macromolecular machines formed by membrane-associated guanylate kinase (MAGUK) scaffold proteins and their interaction partners contributes to variation in intelligence.
Keyword GWAS
Intelligence
NMDA-RC
Pathway analysis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article # e341

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 18 times in Thomson Reuters Web of Science Article | Citations
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