Dataset Information

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

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.

SUBMITTER: Mulligan MK

PROVIDER: S-EPMC1458884 | biostudies-other | 2006 Apr

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

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

Mulligan Megan K MK Ponomarev Igor I Hitzemann Robert J RJ Belknap John K JK Tabakoff Boris B Harris R Adron RA Crabbe John C JC Blednov Yuri A YA Grahame Nicholas J NJ Phillips Tamara J TJ Finn Deborah A DA Hoffman Paula L PL Iyer Vishwanath R VR Koob George F GF Bergeson Susan E SE

Proceedings of the National Academy of Sciences of the United States of America 20060417 16

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 ge ...[more]

PMID: 16618939

Similar Datasets

Project description:Background and aimsEmerging evidence suggests that solitary drinking may be an important early risk marker for alcohol use disorder. The current paper is the first meta-analysis and systematic review on adolescent and young adult solitary drinking to examine associations between solitary drinking and increased alcohol consumption, alcohol problems, and drinking to cope motives.MethodsPsychINFO, PubMed, and Google Scholar were searched using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology and a pre-registered International Prospective Register of Systematic Reviews (PROSPERO) protocol (no. CRD42020143449). Data from self-report questionnaires regarding negative correlates of solitary drinking (e.g. alcohol problems) and solitary drinking motives (e.g. drinking to cope) were pooled across studies using random-effects models. Studies included adolescents (aged 12-18 years) and young adults (mean age between 18 and 30 years or samples with the majority of participants aged 30 years or younger).ResultsMeta-analytical results from 21 unique samples including 28,372 participants showed significant effects for the associations between solitary drinking and the following factors: increased alcohol consumption, r = 0.23, 95% confidence interval (CI) = 0.12, 0.33; drinking problems, r = 0.23, 95% CI = 0.13, 0.32; negative affect, r = 0.21, 95% CI = 0.16, 0.26; social discomfort, r = 0.17, 95% CI = 0.06, 0.27; negative reinforcement, r = 0.28, 95% CI = 0.24, 0.31; and positive reinforcement, r = 0.10, 95% CI = 0.03, 0.17. These associations were not moderated by age group (i.e. adolescent versus young adult), study quality, or differing solitary drinking definitions. Accounting for publication bias increased the effect sizes from r = 0.23 to 0.34 for alcohol consumption and from r = 0.23 to 0.30 for drinking problems, and lowered it from r = 0.10 to 0.06 and r = 0.17 to 0.11 for positive reinforcement and social discomfort, respectively.ConclusionsSolitary drinking among adolescents and young adults appears to be associated with psychosocial/alcohol problems and drinking to cope motives.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets