The androgen receptor gene: A major modifier of speed of neuronal transmission and intelligence?

Summary Humans show considerable additive genetic variance in cognitive ability or general intelligence ( g ) but the genes that influence this variation are largely unknown. It is suggested here that the X-linked androgen receptor gene (AR) has a major modifying effect on speed of neuronal transmis...

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Bibliographic Details
Published in:Medical hypotheses 2007-01, Vol.68 (4), p.802-804
Main Author: Manning, J.T
Format: Article
Language:English
Subjects:
Animals
Gene Expression Regulation
Humans
Intelligence
Internal Medicine
Male
Models, Biological
Models, Neurological
Neurons - metabolism
Neurons - pathology
Peptides - genetics
Primates
Receptors, Androgen - genetics
Spermatozoa - metabolism
Synaptic Transmission
Transcriptional Activation
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Summary:Summary Humans show considerable additive genetic variance in cognitive ability or general intelligence ( g ) but the genes that influence this variation are largely unknown. It is suggested here that the X-linked androgen receptor gene (AR) has a major modifying effect on speed of neuronal transmission and thus on g . The AR is polymorphic in its N-terminal transactivation domain which encodes a polyglutamine tract (CAG n ) with a parametric mean of n = 21 CAG repeats and normal variation between n = 11 and n = 30 repeats . Very low repeat numbers are associated with mental retardation, repeat numbers above 30 with reduced cognitive function, and CAG n greater than 40 with spinal and bulbar muscular atrophy. Within the range of 11–30 repeats short CAG chains are associated with high androgen sensitivity and high sperm counts. Despite this, all human populations contain many individuals with n > 21 repeats. I suggest that within the range of 11–30 repeats there is a positive association with speed of neuronal transmission and values of g . The advantage of high g and the consequent spread of alleles for high CAG n will be countered by the negative effects on sperm production. Below CAG n = 11 and above CAG n = 30 neuronal speed may reduce, thus leading to reductions in g and loss of function of neurons. In support of the model I discuss the link between the X-chromosome and g , the comparative structure of the AR gene in the primates, and the variation in CAG n and g in human ethnic groups.
ISSN:0306-9877
1532-2777
DOI:10.1016/j.mehy.2006.09.014