Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Genetical genomic determinants of alcohol consumption in rats and humans

[thumbnail of 10556oa.pdf] PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB

Item Type:Review
Title:Genetical genomic determinants of alcohol consumption in rats and humans
Creators Name:Tabakoff, B., Saba, L., Printz, M., Flodman, P., Hodgkinson, C., Goldman, D., Koob, G., Richardson, H.N., Kechris, K., Bell, R.L., Huebner, N., Heinig, M., Pravenec, M., Mangion, J., Legault, L., Dongier, M., Conigrave, K.M., Whitfield, J.B., Saunders, J., Grant, B. and Hoffman, P.L.
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. CONCLUSIONS: 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.
Keywords:Alcohol Drinking, Brain, Brain Chemistry, Animal Disease Models, Ethanol, Food Preferences, Gene Expression Profiling, Genetic Predisposition to Disease, Genomics, Microarray Analysis, Phenotype, Single Nucleotide Polymorphism, Quantitative Trait Loci, Heritable Quantitative Trait, Species Specificity, Animals, Rats
Source:BMC Biology
ISSN:1741-7007
Publisher:BioMed Central
Volume:7
Number:1
Page Range:70
Date:27 October 2009
Official Publication:https://doi.org/10.1186/1741-7007-7-70
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library