Evidence map›Paper›PMID 26381263›Full record

ArticlePloS one2015

Integrating mRNA and miRNA Weighted Gene Co-Expression Networks with eQTLs in the Nucleus Accumbens of Subjects with Alcohol Dependence.

Mohammed Mamdani, Vernell Williamson, Gowon O McMichael, Tana Blevins, Fazil Aliev, Amy Adkins, Laura Hack, Tim Bigdeli, Andrew D van der Vaart, Bradley Todd Web and 9 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 5% 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

60 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.

  1. Role of microRNAs in the pathophysiology of addiction.Wiley interdisciplinary reviews. RNA · 2021
    Pooled it
  2. Article
  3. Article
  4. Article
  5. Adaptations in glutathione-based redox protein signaling pathways and alcohol drinking across species.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Noncoding RNA therapeutics for substance use disorder.Advances in drug and alcohol research · 2022
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
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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

19 authors at 2 institutions in 2 countries.

Mohammed MamdaniVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States of America.
Vernell WilliamsonVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States of America.
Gowon O McMichaelVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States of America.
Tana BlevinsDepartment of Pathology, Virginia Commonwealth University, Richmond, VA, United States of America.
Fazil AlievVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States of America; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, United States of America.
Amy AdkinsVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States of America.
Laura HackVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States of America.
Tim BigdeliVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States of America.
Andrew D van der VaartDepartment of Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, VA, United States of America.
Bradley Todd WebVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States of America.
Silviu-Alin BacanuVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States of America.
Gursharan KalsiDepartment of Social, Genetic and Developmental Psychiatry, Institute of Psychiatry, London SE5 8AF, United Kingdom.
COGA Consortium
Kenneth S KendlerVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States of America; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, United States of America; Department of Human & Molecular Genetics, Virginia Commonwealth University, Richmond, VA, United States of America.
Michael F MilesVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States of America; Department of Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, VA, United States of America.
Danielle DickVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States of America; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, United States of America; Department of Human & Molecular Genetics, Virginia Commonwealth University, Richmond, VA, United States of America; Department of Psychology, Virginia Commonwealth University, Richmond, VA, United States of America.
Brien P RileyVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States of America; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, United States of America; Department of Human & Molecular Genetics, Virginia Commonwealth University, Richmond, VA, United States of America.
Catherine DumurDepartment of Pathology, Virginia Commonwealth University, Richmond, VA, United States of America.
Vladimir I VladimirovVirginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States of America; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, United States of America; Center for Biomarker Research and Personalized Medicine, Virginia Commonwealth University, Richmond, VA, United States of America; Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, MD, United States of America.
Virginia Commonwealth University · USPsychiatry Research Trust · GB

Funding

Subject CollectionU10AA008401 · NIAAA · SUNY DOWNSTATE MEDICAL CENTER · PI JESSICA E SALVATORE · 1989 to 2026
$162.7M
JH/CIDR Genotyping for Genome-Wide Association StudiesU01HG004438 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2007 to 2011
$24.2M
Project 5 - Genetic architecture of alcohol use disorder using cross-trait genetic correlations and public next-generation sequencing studiesP50AA022537 · NIAAA · VIRGINIA COMMONWEALTH UNIVERSITY · PI JILL C BETTINGER · 2014 to 2026
$19.6M
Brain Tissue Resource Centre for Alcohol ResearchR28AA012725 · NIAAA · UNIVERSITY OF SYDNEY · PI Greg Trevor Sutherland · 2012 to 2026
$7.0M
Research Training: Psychiatric &Statistical GeneticsT32MH020030 · NIMH · VIRGINIA COMMONWEALTH UNIVERSITY · PI HERMINE H MAES, MICHAEL CHURTON NEALE · 1999 to 2026
$6.7M
Project 3: Cross Species Characterization of Gene Networks in Acute ResponsesP20AA017828 · NIAAA · VIRGINIA COMMONWEALTH UNIVERSITY · PI BETTINGER, JILL C · 2009 to 2012
$2.2M
Cross-species genetic analysis of ethanol-related behaviorR01AA020634 · NIAAA · VIRGINIA COMMONWEALTH UNIVERSITY · PI GROTEWIEL, MICHAEL S., MILES, MICHAEL F · 2012 to 2016
$1.3M
Twin, molecular, and developmental approaches to understanding alcohol misuseK02AA018755 · NIAAA · VIRGINIA COMMONWEALTH UNIVERSITY · PI DICK, DANIELLE M · 2010 to 2019
$1.3M
Integrating miRNAs and mRNAs with alcohol eQTLs in two postmortem brain regionsR21AA022749 · NIAAA · VIRGINIA COMMONWEALTH UNIVERSITY · PI VLADIMIROV, VLADIMIR IVANOV · 2015 to 2016
$400k
Using novel eQTL-based methods to find the molecular causes of alcohol dependencyR21AA022717 · NIAAA · VIRGINIA COMMONWEALTH UNIVERSITY · PI BACANU, SILVIU-ALIN · 2014 to 2015
$382k
NHGRI NIH HHS HHSN268200782096CNHGRI NIH HHS U01 HG004438NHGRI NIH HHS U01HG004438NIAAA NIH HHS 1R21AA022717NIAAA NIH HHS K02 AA018755NIAAA NIH HHS K02AA018755NIAAA NIH HHS P20 AA017828NIAAA NIH HHS P20AA017828NIAAA NIH HHS P50 AA022537NIAAA NIH HHS P50AA022537NIAAA NIH HHS R01 AA020634NIAAA NIH HHS R21 AA022717NIAAA NIH HHS R21 AA022749NIAAA NIH HHS R28 AA012725NIAAA NIH HHS U10 AA008401NIAAA NIH HHS U10AA008401NIAAA NIH HHS VIVU10AA008401NIMH NIH HHS 5T32MH020030NIMH NIH HHS T32 MH020030
6 · The paper itself

Abstract

Alcohol consumption is known to lead to gene expression changes in the brain. After performing weighted gene co-expression network analyses (WGCNA) on genome-wide mRNA and microRNA (miRNA) expression in Nucleus Accumbens (NAc) of subjects with alcohol dependence (AD; N = 18) and of matched controls (N = 18), six mRNA and three miRNA modules significantly correlated with AD were identified (Bonferoni-adj. p≤ 0.05). Cell-type-specific transcriptome analyses revealed two of the mRNA modules to be enriched for neuronal specific marker genes and downregulated in AD, whereas the remaining four mRNA modules were enriched for astrocyte and microglial specific marker genes and upregulated in AD. Gene set enrichment analysis demonstrated that neuronal specific modules were enriched for genes involved in oxidative phosphorylation, mitochondrial dysfunction and MAPK signaling. Glial-specific modules were predominantly enriched for genes involved in processes related to immune functions, i.e. cytokine signaling (all adj. p≤ 0.05). In mRNA and miRNA modules, 461 and 25 candidate hub genes were identified, respectively. In contrast to the expected biological functions of miRNAs, correlation analyses between mRNA and miRNA hub genes revealed a higher number of positive than negative correlations (χ2 test p≤ 0.0001). Integration of hub gene expression with genome-wide genotypic data resulted in 591 mRNA cis-eQTLs and 62 miRNA cis-eQTLs. mRNA cis-eQTLs were significantly enriched for AD diagnosis and AD symptom counts (adj. p = 0.014 and p = 0.024, respectively) in AD GWAS signals in a large, independent genetic sample from the Collaborative Study on Genetics of Alcohol (COGA). In conclusion, our study identified putative gene network hubs coordinating mRNA and miRNA co-expression changes in the NAc of AD subjects, and our genetic (cis-eQTL) analysis provides novel insights into the etiological mechanisms of AD.

Indexed as

Gene Regulatory NetworksQuantitative Trait LociAlcoholismAstrocytesFemaleGene Expression ProfilingHumansMaleMicroRNAsMiddle AgedNeuronsNucleus AccumbensRNA, MessengerSignal TransductionTranscriptomeUp-RegulationMicroRNAsRNA, Messenger

Identifiers

PMID26381263
PMCPMC4575063
OpenAlexW2203621986

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.