Genetical genomic determinants of alcohol consumption in rats and humans

Boris Tabakoff, Laura Saba, Morton Printz, Pam Flodman, Colin Hodgkinson, David Goldman, George Koob, Heather N. Richardson, Katerina Kechris, Richard Bell, Norbert Hübner, Matthias Heinig, Michal Pravenec, Jonathan Mangion, Lucie Legault, Maurice Dongier, Katherine M. Conigrave, John B. Whitfield, John Saunders, Bridget GrantPaula L. Hoffman

Research output: Contribution to journalArticle

118 Citations (Scopus)

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.

Original languageEnglish
Article number1741
Pages (from-to)70
Number of pages1
JournalBMC Biology
Volume7
DOIs
StatePublished - Oct 27 2009

Fingerprint

Alcohol Drinking
Rats
alcohol
genomics
Alcohols
rats
Genes
human population
gene
GABA Receptors
Polymorphism
genes
Energy Intake
gamma-aminobutyric acid
gamma-Aminobutyric Acid
polymorphism
Animal Models
Inbred Strains Rats
Gene expression
Population

ASJC Scopus subject areas

  • Physiology
  • Biotechnology
  • Structural Biology
  • Developmental Biology
  • Plant Science
  • Ecology, Evolution, Behavior and Systematics
  • Cell Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Tabakoff, B., Saba, L., Printz, M., Flodman, P., Hodgkinson, C., Goldman, D., ... Hoffman, P. L. (2009). Genetical genomic determinants of alcohol consumption in rats and humans. BMC Biology, 7, 70. [1741]. https://doi.org/10.1186/1741-7007-7-70

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; Hübner, Norbert; Heinig, Matthias; Pravenec, Michal; Mangion, Jonathan; Legault, Lucie; Dongier, Maurice; Conigrave, Katherine M.; Whitfield, John B.; Saunders, John; Grant, Bridget; Hoffman, Paula L.

In: BMC Biology, Vol. 7, 1741, 27.10.2009, p. 70.

Research output: Contribution to journalArticle

Tabakoff, B, Saba, L, Printz, M, Flodman, P, Hodgkinson, C, Goldman, D, Koob, G, Richardson, HN, Kechris, K, Bell, R, Hübner, N, Heinig, M, Pravenec, M, Mangion, J, Legault, L, Dongier, M, Conigrave, KM, Whitfield, JB, Saunders, J, Grant, B & Hoffman, PL 2009, 'Genetical genomic determinants of alcohol consumption in rats and humans', BMC Biology, vol. 7, 1741, pp. 70. https://doi.org/10.1186/1741-7007-7-70
Tabakoff B, Saba L, Printz M, Flodman P, Hodgkinson C, Goldman D et al. Genetical genomic determinants of alcohol consumption in rats and humans. BMC Biology. 2009 Oct 27;7:70. 1741. https://doi.org/10.1186/1741-7007-7-70
Tabakoff, Boris ; Saba, Laura ; Printz, Morton ; Flodman, Pam ; Hodgkinson, Colin ; Goldman, David ; Koob, George ; Richardson, Heather N. ; Kechris, Katerina ; Bell, Richard ; Hübner, Norbert ; Heinig, Matthias ; Pravenec, Michal ; Mangion, Jonathan ; Legault, Lucie ; Dongier, Maurice ; Conigrave, Katherine M. ; Whitfield, John B. ; Saunders, John ; Grant, Bridget ; Hoffman, Paula L. / Genetical genomic determinants of alcohol consumption in rats and humans. In: BMC Biology. 2009 ; Vol. 7. pp. 70.
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