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Functional Gene Group Analysis Reveals a Role of Synaptic Heterotrimeric G Proteins
 

Summary: ARTICLE
Functional Gene Group Analysis Reveals
a Role of Synaptic Heterotrimeric G Proteins
in Cognitive Ability
Dina Ruano,3 Gonc¸alo R. Abecasis,5 Beate Glaser,4 Esther S. Lips,1 L. Niels Cornelisse,1
Arthur P.H. de Jong,1 David M. Evans,4 George Davey Smith,4 Nicolas J. Timpson,4
August B. Smit,2 Peter Heutink,3 Matthijs Verhage,1 and Danielle Posthuma1,3,*
Although cognitive ability is a highly heritable complex trait, only a few genes have been identified, explaining relatively low propor-
tions 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 (PEMP ¼ 1.9 3 10À4
). 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.

  

Source: Abecasis, Goncalo - Department of Biostatistics, University of Michigan

 

Collections: Biology and Medicine; Mathematics