Publication Details

Toward understanding the genetics of alcohol drinking through transcriptome meta-analysis.

Authors:Mulligan MK, Ponomarev I, Hitzemann RJ, Belknap JK, Tabakoff B, Harris RA, Crabbe JC, Blednov YA, Grahame NJ, Phillips TJ, Finn DA, Hoffman PL, Iyer VR, Koob GF, Bergeson SE
Title:Toward understanding the genetics of alcohol drinking through transcriptome meta-analysis.
Journal:Proceedings of the National Academy of Sciences of the United States of America Apr 2006 , Vol 103 , pp. 6368-73
Abstract:Much evidence from studies in humans and animals supports the hypothesis that alcohol addiction is a complex disease with both hereditary and environmental influences. Molecular determinants of excessive alcohol consumption are difficult to study in humans. However, several rodent models show a high or low degree of alcohol preference, which provides a unique opportunity to approach the molecular complexities underlying the genetic predisposition to drink alcohol. Microarray analyses of brain gene expression in three selected lines, and six isogenic strains of mice known to differ markedly in voluntary alcohol consumption provided >4.5 million data points for a meta-analysis. A total of 107 arrays were obtained and arranged into six experimental data sets, allowing the identification of 3,800 unique genes significantly and consistently changed between all models of high or low amounts of alcohol consumption. Several functional groups, including mitogen-activated protein kinase signaling and transcription regulation pathways, were found to be significantly overrepresented and may play an important role in establishing a high level of voluntary alcohol drinking in these mouse models. Data from the general meta-analysis was further filtered by a congenic strain microarray set, from which cis-regulated candidate genes for an alcohol preference quantitative trait locus on chromosome 9 were identified: Arhgef12, Carm1, Cryab, Cox5a, Dlat, Fxyd6, Limd1, Nicn1, Nmnat3, Pknox2, Rbp1, Sc5d, Scn4b, Tcf12, Vps11, and Zfp291 and four ESTs. The present study demonstrates the use of (i) a microarray meta-analysis to analyze a behavioral phenotype (in this case, alcohol preference) and (ii) a congenic strain for identification of cis regulation.   PUBMED: 16618939
Ontological Annotations:
  • D012377: Rodentia (Publication, NCBO Annotator)
  • D032882: Comprehension (Publication, NCBO Annotator)
  • D006801: Humans (Publication, NCBO Annotator; PubMed MeSH Annotations)
  • D002875: Chromosomes (Publication, NCBO Annotator)
  • D020411: Oligonucleotide Array Sequence Analysis (PubMed MeSH Annotations)
  • D000818: Animals (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • GO:0005694: chromosome (Publication, NCBO Annotator)
  • D004326: Drinking (Publication, NCBO Annotator)
  • D020224: Expressed Sequence Tags (Publication, NCBO Annotator)
  • D010988: Play and Playthings (Publication, NCBO Annotator)
  • D001921: Brain (Publication, NCBO Annotator; PubMed MeSH Annotations)
  • D012380: Role (Publication, NCBO Annotator)
  • MP:0002555: addiction (Publication, NCBO Annotator)
  • D005786: Gene Expression Regulation (PubMed MeSH Annotations)
  • D009838: Oligodeoxyribonucleotides (PubMed MeSH Annotations)
  • D020022: Genetic Predisposition to Disease (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D012926: Social Control, Formal (Publication, NCBO Annotator)
  • MA:0000168: brain (Publication, NCBO Annotator)
  • MP:0001987: alcohol preference (Publication, NCBO Annotator)
  • D011494: Protein Kinases (Publication, NCBO Annotator)
  • D012718: Set (Psychology) (Publication, NCBO Annotator)
  • D008815: Mice, Inbred Strains (PubMed MeSH Annotations)
  • D002899: Chromosomes, Human, Pair 9 (Publication, NCBO Annotator)
  • D005823: Genetics (Publication, NCBO Annotator)
  • D017418: Meta-Analysis (Publication, NCBO Annotator)
  • D040641: Quantitative Trait Loci (Publication, NCBO Annotator; PubMed MeSH Annotations)
  • D000428: Alcohol Drinking (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D007062: Identification (Psychology) (Publication, NCBO Annotator)
  • GO:0023052: signaling (Publication, NCBO Annotator)
  • D051379: Mice (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D000437: Alcoholism (PubMed MeSH Annotations)
  • GO:0010467: gene expression (Publication, NCBO Annotator)
  • D010770: Phosphotransferases (Publication, NCBO Annotator)
  • D014158: Transcription, Genetic (PubMed MeSH Annotations)

2 GeneSets from this Publication:

Select gene sets below using the check boxes, and then add them to a project using the pull down below. You can also create a project using the pull down. To view a set, click on the GeneSetID:GeneSet Description shown in green below.
Expand Tier IV Mouse 3169 Genes GS3647: Meta-analysis of brain gene expression associated with voluntary consumption of ethanol in mice
Expand Tier II Mouse 610 Genes GS135821: ethanol consumption 3 (Etohc3, Published QTL Chr 9)