Evidence map›Paper›PMID 30862775›Full record

ArticleTranslational psychiatry2019

Alcohol-responsive genes identified in human iPSC-derived neural cultures.

Kevin P Jensen, Richard Lieberman, Henry R Kranzler, Joel Gelernter, Kaitlin Clinton, Jonathan Covault

Open access · goldAbstract read
In one paragraph

Article in Translational psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.2field-weighted citation impact, top 25% 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

17 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
  2. Article
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  4. Article
  5. Upregulated GIRK2 Counteracts Ethanol-Induced Changes in Excitability and Respiration in Human Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
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  7. Review
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  9. Review
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  12. Induced pluripotent stem cell reprogramming-associated methylation at the GABRA2 promoter and chr4p12 GABAAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2020
    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

6 authors at 3 institutions in 1 country.

Kevin P JensenDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, 06511, USA.
Richard LiebermanAlcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, 06030-1410, USA.
Henry R KranzlerCenter for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, 19104, USA.ORCID http://orcid.org/0000-0002-1018-0450
Joel GelernterDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, 06511, USA.ORCID http://orcid.org/0000-0002-4067-1859
Kaitlin ClintonAlcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, 06030-1410, USA.
Jonathan CovaultAlcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, 06030-1410, USA. jocovault@uchc.edu.
University of Connecticut · USYale University · USPhiladelphia VA Medical Center · US

Funding

ZONISAMIDE VERSUS PLACEBOM01RR006192 · NCRR · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI LAURENCIN, CATO T. · 1994 to 2008
$22.1M
Vulnerabilities for coping-related drinking among post-college young adultsP60AA003510 · NIAAA · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI HESSELBROCK, VICTOR M · 2008 to 2017
$17.5M
Pilot StudiesP50AA027055 · NIAAA · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI COVAULT, JONATHAN M · 2019 to 2023
$7.8M
Pharmacogenetic Analysis of Topiramate Treatment of AUDR01AA023192 · NIAAA · UNIVERSITY OF PENNSYLVANIA · PI KRANZLER, HENRY RICHARD · 2014 to 2018
$2.7M
Pharmacogenetics of Alcohol: Treatment ImplicationsR01AA015606 · NIAAA · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI COVAULT, JONATHAN M · 2006 to 2009
$1.8M
Pharmacogenetics of alcohol treatment: Topiramate and GRIK1R21AA023212 · NIAAA · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI COVAULT, JONATHAN M · 2014 to 2015
$417k
NCRR NIH HHS M01 RR006192NIAAA NIH HHS P50 AA027055NIAAA NIH HHS P60 AA003510NIAAA NIH HHS R01 AA015606NIAAA NIH HHS R01 AA023192NIAAA NIH HHS R21 AA023212
6 · The paper itself

Abstract

Alcohol use contributes to numerous diseases and injuries. The nervous system is affected by alcohol in diverse ways, though the molecular mechanisms of these effects are not clearly understood. Using human-induced pluripotent stem cells (iPSCs), we developed a neural cell culture model to identify the mechanisms of alcohol's effects. iPSCs were generated from fibroblasts and differentiated into forebrain neural cells cultures that were treated with 50 mM alcohol or sham conditions (same media lacking alcohol) for 7 days. We analyzed gene expression using total RNA sequencing (RNA-seq) for 34 samples derived from 10 subjects and for 10 samples from 5 subjects in an independent experiment that had intermittent exposure to the same dose of alcohol. We also analyzed genetic effects on gene expression and conducted a weighted correlation network analysis. We found that differentiated neural cell cultures have the capacity to recapitulate gene regulatory effects previously observed in specific primary neural tissues and identified 226 genes that were differentially expressed (FDR < 0.1) after alcohol treatment. The effects on expression included decreases in INSIG1 and LDLR, two genes involved in cholesterol homeostasis. We also identified a module of 58 co-expressed genes that were uniformly decreased following alcohol exposure. The majority of these effects were supported in independent alcohol exposure experiments. Enrichment analysis linked the alcohol responsive genes to cell cycle, notch signaling, and cholesterol biosynthesis pathways, which are disrupted in several neurological disorders. Our findings suggest that there is convergence between these disorders and the effects of alcohol exposure.

Indexed as

AdultAlcoholismCase-Control StudiesCell DifferentiationCells, CulturedEthanolFemaleGene Expression ProfilingHumansInduced Pluripotent Stem CellsMaleMiddle AgedNeural Stem CellsYoung AdultEthanol

Identifiers

PMID30862775
PMCPMC6414668
OpenAlexW2949211300

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.