Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
19874574
TITLE
Genetical genomic determinants of alcohol consumption in rats and humans.
ABSTRACT
BACKGROUND NlmCategory: 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 NlmCategory: 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 NlmCategory: 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.
DATE PUBLISHED
2009
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2009/09/29
accepted 2009/10/27
aheadofprint 2009/10/27
entrez 2009/10/31 06:00
pubmed 2009/10/31 06:00
medline 2010/01/16 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Tabakoff B Tabakoff Boris B Department of Pharmacology, University of Colorado, Denver, Aurora, CO, USA. boris.tabakoff@ucdenver.edu
Saba L Saba Laura L
Printz M Printz Morton M
Flodman P Flodman Pam P
Hodgkinson C Hodgkinson Colin C
Goldman D Goldman David D
Koob G Koob George G
Richardson HN Richardson Heather N HN
Kechris K Kechris Katerina K
Bell RL Bell Richard L RL
Hübner N Hübner Norbert N
Heinig M Heinig Matthias M
Pravenec M Pravenec Michal M
Mangion J Mangion Jonathan J
Legault L Legault Lucie L
Dongier M Dongier Maurice M
Conigrave KM Conigrave Katherine M KM
Whitfield JB Whitfield John B JB
Saunders J Saunders John J
Grant B Grant Bridget B
Hoffman PL Hoffman Paula L PL
WHO/ISBRA Study on State and Trait Markers of Alcoholism
INVESTIGATORS
JOURNAL
VOLUME: 7
ISSUE:
TITLE: BMC biology
ISOABBREVIATION: BMC Biol.
YEAR: 2009
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1741-7007
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: BMC Biol
COUNTRY: England
ISSNLINKING: 1741-7007
NLMUNIQUEID: 101190720
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):2053-8 12566570
Cites Alcohol Clin Exp Res. 2003 Feb;27(2):220-31 12605071
Cites Bioinformatics. 2003 May 1;19(7):889-90 12724300
Cites J Biol Chem. 2003 May 9;278(19):17509-14 12615930
Cites J Appl Physiol (1985). 2003 Jun;94(6):2510-22 12736193
Cites J Neurosci. 2003 Jun 1;23(11):4491-8 12805289
Cites J Neurocytol. 2002 Mar-Jun;31(3-5):277-87 12815247
Cites Mamm Genome. 2003 Jul;14(7):454-63 12925894
Cites Arch Gen Psychiatry. 2003 Dec;60(12):1256-64 14662558
Cites Nature. 2003 Dec 18;426(6968):789-96 14685227
Cites BMC Genet. 2003;4 Suppl 1:S101 14975169
Cites Science. 2004 Mar 5;303(5663):1512-4 15001778
Cites Neurosci Biobehav Rev. 2004 Jan;27(8):765-76 15019426
Cites Neuron. 2004 Sep 30;44(1):161-79 15450168
Cites Genome Biol. 2004;5(10):R80 15461798
Cites Behav Genet. 1977 Nov;7(6):413-25 603475
Cites Life Sci. 1987 Jun 1;40(22):2191-4 3586856
Cites Alcohol. 1990 May-Jun;7(3):187-91 2184831
Cites J Neurochem. 1991 Apr;56(4):1409-16 2002350
Cites Trends Pharmacol Sci. 1992 May;13(5):177-84 1604710
Cites Genetics. 1994 Nov;138(3):963-71 7851788
Cites Alcohol Clin Exp Res. 2009 Mar;33(3):531-7 19120064
Cites Neuron. 2009 Mar 12;61(5):786-800 19285474
Cites Alcohol Clin Exp Res. 2009 Apr;33(4):729-39 19183129
Cites Int J Obes (Lond). 2009 Jun;33 Suppl 2:S18-24 19528974
Cites Am J Physiol Endocrinol Metab. 2009 Jul;297(1):E10-8 19116371
Cites Arch Gen Psychiatry. 2009 Jul;66(7):773-84 19581569
Cites Proc Natl Acad Sci U S A. 2009 Jul 7;106(27):11318-23 19564604
Cites BMC Genet. 2005;6 Suppl 1:S112 16451569
Cites Neuron. 1999 Sep;24(1):155-63 10677034
Cites J Neurosci. 2000 Mar 15;20(6):2121-30 10704486
Cites Trends Neurosci. 2000 Sep;23(9):429-35 10941193
Cites Neurosci Lett. 2000 Nov 3;293(3):167-70 11036187
Cites Alcohol. 2001 Jan;23(1):41-8 11282451
Cites BMC Genet. 2005;6:11 15740611
Cites Eur J Neurosci. 2005 Apr;21(7):1837-46 15869479
Cites Eur J Neurosci. 2005 Apr;21(8):2233-42 15869520
Cites Bioinformatics. 2005 May 15;21(10):2383-93 15613385
Cites Mol Pharmacol. 2005 Jul;68(1):152-9 15814572
Cites Alcohol Clin Exp Res. 2005 Jun;29(6):949-57 15976520
Cites J Comp Neurol. 2005 Sep 19;490(2):119-32 16052498
Cites J Neurosci. 2005 Oct 19;25(42):9746-51 16237178
Cites Mol Endocrinol. 1994 Oct;8(10):1298-308 7854347
Cites Eur J Pharmacol. 1995 Sep 5;283(1-3):151-9 7498304
Cites Neurosci Biobehav Rev. 1996;20(1):1-25 8622814
Cites Neuron. 1996 May;16(5):909-12 8630248
Cites Pharmacol Biochem Behav. 1996 Apr;53(4):971-7 8801605
Cites Alcohol Clin Exp Res. 1995 Dec;19(6):1486-93 8749815
Cites Genetics. 1996 Jun;143(2):1013-20 8725246
Cites Alcohol. 1996 Jan-Feb;13(1):13-7 8837928
Cites J Neurosci. 1997 Jul 1;17(13):4994-5003 9185537
Cites Pharmacol Biochem Behav. 1997 Oct;58(2):497-504 9300611
Cites Neuropeptides. 1997 Feb;31(1):82-8 9574843
Cites Am J Hum Genet. 1999 Jul;65(1):220-8 10364535
Cites Bioinformatics. 2005 Jan 15;21(2):263-5 15297300
Cites Addiction. 2006 Sep;101 Suppl 1:59-75 16930162
Cites Addict Biol. 2006 Sep;11(3-4):270-88 16961759
Cites Trends Cell Biol. 2006 Oct;16(10):522-9 16949823
Cites J Biol Chem. 2007 Feb 9;282(6):4162-71 17145756
Cites Mol Biol Cell. 2007 Mar;18(3):732-42 17182860
Cites Trends Neurosci. 2007 Aug;30(8):375-81 17604133
Cites Brain Res. 2007 Aug 20;1164:125-31 17640622
Cites Biochem J. 2007 Dec 1;408(2):221-30 17680774
Cites Physiol Genomics. 2007 Nov 14;31(3):410-21 17804602
Cites Neuropeptides. 2007 Dec;41(6):453-63 17904218
Cites Neuropsychopharmacology. 2008 Jan;33(1):166-80 17805308
Cites Brain Res Rev. 2007 Dec;56(2):331-45 17915333
Cites Handb Exp Pharmacol. 2008;(184):435-77 18064422
Cites Drug Alcohol Depend. 2008 Jan 11;93(1-2):12-20 17942244
Cites FEBS Lett. 2008 Jan 9;582(1):132-41 18061579
Cites Alcohol Clin Exp Res. 2008 Feb;32(2):306-13 18162067
Cites PLoS One. 2008;3(3):e1797 18335063
Cites Alcohol. 2008 May;42(3):149-60 18358676
Cites Nat Rev Neurosci. 2008 May;9(5):331-43 18382465
Cites Neuroscience. 2008 Apr 22;153(1):240-8 18343590
Cites Nat Genet. 2008 May;40(5):560-6 18443594
Cites J Neurosci. 2008 May 7;28(19):4957-66 18463249
Cites Br J Pharmacol. 2008 May;154(2):261-74 18311189
Cites Arch Gen Psychiatry. 2008 Jun;65(6):674-82 18519825
Cites Pharmacol Biochem Behav. 2008 Jul;90(1):90-4 18423561
Cites Curr Biol. 2008 Jun 24;18(12):911-4 18571413
Cites Mamm Genome. 2008 May;19(5):352-65 18563486
Cites J Pharmacol Exp Ther. 2008 Sep;326(3):792-800 18550690
Cites Alcohol Alcohol. 2008 Sep-Oct;43(5):505-15 18477577
Cites Drug Alcohol Depend. 2008 Nov 1;98(1-2):105-14 18586414
Cites Endocr Metab Immune Disord Drug Targets. 2008 Sep;8(3):220-30 18782018
Cites Neurobiol Learn Mem. 2008 Oct;90(3):553-9 18644245
Cites J Pharmacol Exp Ther. 2008 Oct;327(1):196-205 18583548
Cites Alcohol Clin Exp Res. 2008 Oct;32(10):1714-20 18627359
Cites Neuropsychopharmacology. 2009 Jan;34(2):509-21 18580872
Cites Neuropharmacology. 2009;56 Suppl 1:18-31 18725236
Cites Alcohol Clin Exp Res. 2008 Dec;32(12):2054-61 18828808
Cites Cell. 2005 Nov 4;123(3):493-505 16269339
Cites Alcohol Clin Exp Res. 2005 Nov;29(11):1939-48 16340450
Cites Peptides. 2006 Jan;27(1):144-9 16198024
Cites Int J Obes (Lond). 2006 Apr;30 Suppl 1:S7-S12 16570107
Cites J Physiol. 2006 Apr 15;572(Pt 2):425-42 16455686
Cites Psychol Med. 2006 Jul;36(7):931-41 16563205
Cites Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8858-63 16723393
Cites Mamm Genome. 2006 Jun;17(6):466-79 16783628
Cites Neuroreport. 2001 Jul 20;12(10):2155-8 11447325
Cites Nutrition. 2001 Jul-Aug;17(7-8):638-41 11448587
Cites Peptides. 2001 Aug;22(8):1213-21 11457513
Cites Eur J Neurosci. 2001 Aug;14(4):595-608 11556885
Cites Physiol Behav. 2001 Nov-Dec;74(4-5):581-7 11790418
Cites Genome Res. 2002 Apr;12(4):656-64 11932250
Cites J Neurosci. 2002 May 1;22(9):3730-8 11978849
Cites Genome Res. 2002 Jun;12(6):868-84 12045141
Cites Alcohol Clin Exp Res. 2002 Jun;26(6):773-8 12068244
Cites Science. 2002 Jun 21;296(5576):2225-9 12029063
Cites Alcohol Clin Exp Res. 2002 Jul;26(7):1047-61 12170115
Cites Behav Genet. 2002 Sep;32(5):363-88 12405517
Cites J Comp Neurol. 2003 Mar 10;457(3):213-35 12541307
Cites Nucleic Acids Res. 2003 Feb 15;31(4):e15 12582260
GRANTS
GRANTID AGENCY COUNTRY
AA006420 NIAAA NIH HHS United States
AA013162 NIAAA NIH HHS United States
AA013517-INIA NIAAA NIH HHS United States
AA013522-INIA NIAAA NIH HHS United States
AA016649-INIA NIAAA NIH HHS United States
AA016663-INIA NIAAA NIH HHS United States
AA16922 NIAAA NIH HHS United States
HL35018 NHLBI NIH HHS United States
P60 AA006420 NIAAA NIH HHS United States
R24 AA013162 NIAAA NIH HHS United States
R24 AA015512 NIAAA NIH HHS United States
U01 AA013522 NIAAA NIH HHS United States
Howard Hughes Medical Institute United States
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Alcohol Drinking metabolism
Animals metabolism
Brain metabolism
Brain Chemistry metabolism
Disease Models, Animal metabolism
Ethanol administration & dosage
Female administration & dosage
Food Preferences physiology
Gene Expression Profiling physiology
Genetic Predisposition to Disease physiology
Genomics physiology
Humans physiology
Male physiology
Microarray Analysis physiology
Phenotype physiology
Polymorphism, Single Nucleotide physiology
Quantitative Trait Loci physiology
Quantitative Trait, Heritable physiology
Rats physiology
Rats, Inbred Strains physiology
Species Specificity physiology
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
3K9958V90M Ethanol
OTHER ID's
OTHERID SOURCE
PMC2777866 NLM