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Effects of GABRA2 Variation on Physiological, Psychomotor and Subjective Responses in the Alcohol Challenge Twin Study

Published online by Cambridge University Press:  21 February 2012

Penelope A. Lind
Affiliation:
Genetic Epidemiology Unit, Queensland Institute of Medical Research, Brisbane, Australia.
Stuart MacGregor
Affiliation:
Genetic Epidemiology Unit, Queensland Institute of Medical Research, Brisbane, Australia.
Grant W. Montgomery
Affiliation:
Genetic Epidemiology Unit, Queensland Institute of Medical Research, Brisbane, Australia.
Andrew C. Heath
Affiliation:
Missouri Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, United States of America.
Nicholas G. Martin
Affiliation:
Genetic Epidemiology Unit, Queensland Institute of Medical Research, Brisbane, Australia.
John B. Whitfield*
Affiliation:
Genetic Epidemiology Unit, Queensland Institute of Medical Research, Brisbane, Australia. [email protected]
*
1Address for correspondence: Dr J. B. Whitfield, Genetic Epidemiology Unit, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Queensland 4029, Australia.

Abstract

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Multiple reports have identified variation in the GABRA2 gene as contributing to the genetic susceptibility to alcohol dependence. However, both the mechanism behind this association, and the range of alcohol-related phenotypes affected by variation in this gene, are currently undefined. Other data suggest that the risk of alcohol dependence is increased by relative insensitivity to alcohol's intoxicating effects. We have therefore tested whether GABRA2 variation is associated with variation in the subjective and objective effects of a standard dose of alcohol in humans. Data on responses to alcohol from the Alcohol Challenge Twin Study (Martin et al., 1985) have been tested against allelic and haplotype information obtained by typing 41 single-nucleotide polymorphisms in or close to the GABRA2 gene. Nominally significant allelic associations (p < .05, without correction for multiple testing) were found for body sway, motor coordination, pursuit rotor and arithmetical computation tasks, and for the personality dimension of Neuroticism. Because of the large number of phenotypes tested, these possibly significant findings will need to be confirmed in further studies.

Type
Articles
Copyright
Copyright © Cambridge University Press 2008