Genetical genomic determinants of alcohol consumption in rats and humans

Tabakoff, Boris, Saba, Laura, Printz, Morton, Flodman, Pam, Hodgkinson, Colin, Goldman, David, Koob, George, Richardson, Heather N., Kechris, Katerina, Bell, Richard L., Hubner, Norbert, Heinig, Matthias, Pravenec, Michal, Mangion, Jonathan, Legault, Lucie, Dongier, Maurice, Conigrave, Katherine M., Whitfield, John B., Saunders, John, Grant, Bridget, Hoffman, Paula L. and WHO ISBRA Study State Trait Marker (2009) Genetical genomic determinants of alcohol consumption in rats and humans. BMC Biology, 7 70.1-70.23. doi:10.1186/1741-7007-7-70

Author Tabakoff, Boris
Saba, Laura
Printz, Morton
Flodman, Pam
Hodgkinson, Colin
Goldman, David
Koob, George
Richardson, Heather N.
Kechris, Katerina
Bell, Richard L.
Hubner, Norbert
Heinig, Matthias
Pravenec, Michal
Mangion, Jonathan
Legault, Lucie
Dongier, Maurice
Conigrave, Katherine M.
Whitfield, John B.
Saunders, John
Grant, Bridget
Hoffman, Paula L.
WHO ISBRA Study State Trait Marker
Title Genetical genomic determinants of alcohol consumption in rats and humans
Journal name BMC Biology   Check publisher's open access policy
ISSN 1741-7007
Publication date 2009-10-27
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1186/1741-7007-7-70
Open Access Status DOI
Volume 7
Start page 70.1
End page 70.23
Total pages 23
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted abstract
Background: We have used a genetical genomic approach, in conjunction with phenotypic analysis of alcohol consumption, to identify candidate genes that predispose to varying levels of alcohol intake by HXB/BXH recombinant inbred rat strains. In addition, in two populations of humans, we assessed genetic polymorphisms associated with alcohol consumption using a custom genotyping array for 1,350 single nucleotide polymorphisms (SNPs). Our goal was to ascertain whether our approach, which relies on statistical and informatics techniques, and non-human animal models of alcohol drinking behavior, could inform interpretation of genetic association studies with human populations.
Results: In the HXB/BXH recombinant inbred (RI) rats, correlation analysis of brain gene expression levels with alcohol consumption in a two-bottle choice paradigm, and filtering based on behavioral and gene expression quantitative trait locus (QTL) analyses, generated a list of candidate genes. A literature-based, functional analysis of the interactions of the products of these candidate genes defined pathways linked to presynaptic GABA release, activation of dopamine neurons, and postsynaptic GABA receptor trafficking, in brain regions including the hypothalamus, ventral tegmentum and amygdala. The analysis also implicated energy metabolism and caloric intake control as potential influences on alcohol consumption by the recombinant inbred rats. In the human populations, polymorphisms in genes associated with GABA synthesis and GABA receptors, as well as genes related to dopaminergic transmission, were associated with alcohol consumption.
Conclusion: Our results emphasize the importance of the signaling pathways identified using the non-human animal models, rather than single gene products, in identifying factors responsible for complex traits such as alcohol consumption. The results suggest cross-species similarities in pathways that influence predisposition to consume alcohol by rats and humans. The importance of a well-defined phenotype is also illustrated. Our results also suggest that different genetic factors predispose alcohol dependence versus the phenotype of alcohol consumption.
Keyword Ventral tegmental area
Protease-activated receptors
Food intake
Central nervous system
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Article # 70

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
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School of Medicine Publications
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Created: Sun, 29 Nov 2009, 00:05:29 EST