Functional gene-group analysis reveals a role of synaptic heterotrimeric G-proteins in cognitive ability

Dina Ruano, Gonçalo R Abecasis, Beate Glaser, Esther S Lips, L Niels Cornelisse, Arthur P H de Jong, David M Evans, George Davey Smith, Nicholas John Timpson, August B Smit, Peter Heutink, Matthijs Verhage, Danielle Posthuma

Research output: Contribution to journalArticle (Academic Journal)peer-review

89 Citations (Scopus)

Abstract

Although cognitive ability is a highly heritable complex trait, only a few genes have been identified, explaining relatively low proportions of the observed trait variation. This implies that hundreds of genes of small effect may be of importance for cognitive ability. We applied an innovative method in which we tested for the effect of groups of genes defined according to cellular function (functional gene group analysis). Using an initial sample of 627 subjects, this functional gene group analysis detected that synaptic heterotrimeric guanine nucleotide binding proteins (G proteins) play an important role in cognitive ability (P(EMP) = 1.9 x 10(-4)). The association with heterotrimeric G proteins was validated in an independent population sample of 1507 subjects. Heterotrimeric G proteins are central relay factors between the activation of plasma membrane receptors by extracellular ligands and the cellular responses that these induce, and they can be considered a point of convergence, or a "signaling bottleneck." Although alterations in synaptic signaling processes may not be the exclusive explanation for the association of heterotrimeric G proteins with cognitive ability, such alterations may prominently affect the properties of neuronal networks in the brain in such a manner that impaired cognitive ability and lower intelligence are observed. The reported association of synaptic heterotrimeric G proteins with cognitive ability clearly points to a new direction in the study of the genetic basis of cognitive ability.
Translated title of the contributionFunctional gene-group analysis reveals a role of synaptic heterotrimeric G-proteins in cognitive ability
Original languageEnglish
Pages (from-to)113 - 125
Number of pages12
JournalAmerican Journal of Human Genetics
Volume86
Issue number2
DOIs
Publication statusPublished - Feb 2010

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