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- J. Mohr, I. Puls, J. Wrase,
J. Priller, J. Behr, W. Kitzrow, N. Makris, H. Breiter, K. Obermayer, and
A. Heinz. Synergistic effects of the dopaminergic and glutamatergic system
on hippocampal volume in alcohol-dependent patients.
.
Biological Psychology, 79(1), 2008.
Several genes of the dopaminergic and glutamatergic
neurotransmitter systems have been found to be associated with alcohol
disease and related intermediate phenotypes. Here, we evaluated genetic
variants of the catechol-O-methyltransferase and the metabotropic glutamate
receptor 3 gene in alcohol-dependent patients and their association with
volumetric measurements of brain structures. By combined analysis of imaging
data and genotyping results, large numbers of variables are produced that
overstrain conventional statistical methods based on tests for group
differences. Limitations in assessment of epistatic effects and multiple
testing problems are encountered. Therefore, we introduce a novel method for
detecting associations between a set of genetic markers and phenotypical
measurements based on machine learning techniques. Hippocampal volume was
found to be associated with epistatic effects of the COMT-mGluR3 genes in
alcohol-dependent patients but not in controls. These data are in line with
prior studies supporting a role for dopamine-glutamate-interaction in
modulation of alcohol disease.
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