Evidence map›Paper›PMID 23550792›Full record

ArticleAlcoholism, clinical and experimental research2013

Selection for drinking in the dark alters brain gene coexpression networks.

Ovidiu D Iancu, Denesa Oberbeck, Priscila Darakjian, Pamela Metten, Shannon McWeeney, John C Crabbe, Robert Hitzemann

Open access · bronzeAbstract read
In one paragraph

Article in Alcoholism, clinical and experimental research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
7.7field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 72 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Ovidiu D IancuDepartment of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA. iancuo@ohsu.edu
Denesa Oberbeck
Priscila Darakjian
Pamela Metten
Shannon McWeeney
John C Crabbe
Robert Hitzemann
Oregon Health & Science University · USPortland VA Medical Center · US

Funding

Translational measures of risk for excessive alcohol consumptionP60AA010760 · NIAAA · OREGON HEALTH & SCIENCE UNIVERSITY · PI Suzanne S. Fei · 2006 to 2026
$34.5M
Oregon Clinical and Translational Research InstituteUL1TR000128 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI ELLISON, DAVID H · 2012 to 2015
$28.7M
Selective Breeding for Drinking in the Circadian DarkU01AA013519 · NIAAA · OREGON HEALTH & SCIENCE UNIVERSITY · PI Angela Renee Ozburn · 2001 to 2026
$10.9M
THERMAL AND METABOLIC DYSFUNCTION DURING WITHDRAWALP50AA010760 · NIAAA · OREGON HEALTH AND SCIENCE UNIVERSITY · PI CRABBE, JOHN C. · 1996 to 2005
$10.7M
Neurocircuitry Mapping and Genotyping CoreU01AA013484 · NIAAA · OREGON HEALTH & SCIENCE UNIVERSITY · PI HITZEMANN, ROBERT J. · 2001 to 2021
$6.2M
Mapping the Genes for Ethanol-Related PhenotypesR01AA011034 · NIAAA · STATE UNIVERSITY NEW YORK STONY BROOK · PI HITZEMANN, ROBERT J. · 1996 to 2014
$5.1M
GENETIC VULNERABILITY TO DRUGS OF ABUSER01DA005228 · NIDA · OREGON HEALTH & SCIENCE UNIVERSITY · PI BUCK, KARI J · 1989 to 2015
$4.6M
Mouse Genetic Models for Alcohol ResearchR24AA020245 · NIAAA · OREGON HEALTH & SCIENCE UNIVERSITY · PI PHILLIPS, TAMARA J. · 2011 to 2020
$2.3M
NCATS NIH HHS UL1 TR000128NIAAA NIH HHS AA 10760NIAAA NIH HHS AA 13484NIAAA NIH HHS AA 13519NIAAA NIH HHS AA 20245NIAAA NIH HHS P50 AA010760NIAAA NIH HHS P60 AA010760NIAAA NIH HHS R01 AA011034NIAAA NIH HHS R24 AA020245NIAAA NIH HHS U01 AA013484NIAAA NIH HHS U01 AA013519NIDA NIH HHS DA005228NIDA NIH HHS R01 DA005228
6 · The paper itself

Abstract

backgroundHeterogeneous stock (HS/NPT) mice have been used to create lines selectively bred in replicate for elevated drinking in the dark (DID). Both selected lines routinely reach a blood ethanol (EtOH) concentration (BEC) of 1.00 mg/ml or greater at the end of the 4-hour period of access in Day 2. The mechanisms through which genetic differences influence DID are currently unclear. Therefore, the current study examines the transcriptome, the first stage at which genetic variability affects neurobiology. Rather than focusing solely on differential expression (DE), we also examine changes in the ways that gene transcripts collectively interact with each other, as revealed by changes in coexpression patterns.

methodsNaïve mice (N = 48/group) were genotyped using the Mouse Universal Genotyping Array, which provided 3,683 informative markers. Quantitative trait locus (QTL) analysis used a marker-by-marker strategy with the threshold for a significant logarithm of odds (LOD) set at 10.6. Gene expression in the ventral striatum was measured using the Illumina Mouse 8.2 array. Differential gene expression and the weighted gene coexpression network analysis (WGCNA) were implemented largely as described elsewhere.

resultsSignificant QTLs for elevated BECs after DID were detected on chromosomes 4, 14, and 16; the latter 2 were associated with gene-poor regions. None of the QTLs overlapped with known QTLs for EtOH preference drinking. Ninety-four transcripts were detected as being differentially expressed in both selected lines versus HS controls; there was no overlap with known preference genes. The WGCNA revealed 2 modules as showing significant effects of both selections on intramodular connectivity. A number of genes known to be associated with EtOH phenotypes (e.g., Gabrg1, Glra2, Grik1, Npy2r, and Nts) showed significant changes in connectivity.

conclusionsWe found marked and consistent effects of selection on coexpression patterns; DE changes were more modest and less concordant. The QTLs and differentially expressed genes detected here are distinct from the preference phenotype. This is consistent with behavioral data and suggests that the DID and preference phenotypes are markedly different genetically.

Indexed as

Selection, GeneticAlcohol DrinkingAnimalsBasal GangliaBrain ChemistryDarknessFemaleGene Regulatory NetworksMaleMiceQuantitative Trait LociAlcoholBingeDrinking in the DarkMicroarrayMouseSelectionWeighted Gene Coexpression Network Analysis

Identifiers

PMID23550792
PMCPMC3759151
OpenAlexW2021261685

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.