Evidence map›Paper›PMID 28072409›Full record

ArticleTranslational psychiatry2017

Alcohol-dose-dependent DNA methylation and expression in the nucleus accumbens identifies coordinated regulation of synaptic genes.

R Cervera-Juanes, L J Wilhelm, B Park, K A Grant, B Ferguson

Open access · goldAbstract read
In one paragraph

Article in Translational psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 10% 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

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. EpiBrain: the brain's epigenetic landscape in a snapshot.bioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Alcohol and the brain: from genes to circuits.Trends in neurosciences · 2021
    Review
  16. Article
  17. Role of GPR39 in Neurovascular Homeostasis and Disease.International journal of molecular sciences · 2021
    Review
  18. Article
  19. Article
  20. Chronic ethanol consumption alters lamina propria leukocyte response to stimulation in a region-dependent manner.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
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

5 authors at 2 institutions in 1 country.

R Cervera-JuanesDepartment of Neurosciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.
L J WilhelmDepartment of Neurosciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.
B ParkDepartment of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, OR, USA.
K A GrantDepartment of Neurosciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.
B FergusonDepartment of Neurosciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.ORCID 0000-0002-6992-3538
Oregon National Primate Research Center · USOregon Health & Science University · US

Funding

Upgrade of confocal microscopy at the Oregon National Primate Research CenterP51OD011092 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI Bonnie J. Nagel · 2012 to 2026
$203.9M
Stress and Ethanol Self-Administration in MonkeysU01AA013510 · NIAAA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI KATHLEEN A GRANT · 2002 to 2026
$11.8M
Monkey Alcohol Tissue Research Resource (MATRR)R24AA019431 · NIAAA · OREGON HEALTH & SCIENCE UNIVERSITY · PI Mary Lauren Benton, Verginia Carmella Cuzon Carlson · 2010 to 2026
$10.3M
INIA: Stress, Anxiety and Excessive Alcohol Drinking (Administrative Core)U24AA013641 · NIAAA · OREGON HEALTH & SCIENCE UNIVERSITY · PI KATHLEEN A GRANT · 2016 to 2026
$3.4M
Genetic and Epigenetic Analysis of Alcohol Self-Administration in MonkeysU01AA020928 · NIAAA · OREGON HEALTH & SCIENCE UNIVERSITY · PI FERGUSON, BETSY M · 2012 to 2016
$1.3M
NIAAA NIH HHS R24 AA019431NIAAA NIH HHS U01 AA013510NIAAA NIH HHS U01 AA020928NIAAA NIH HHS U24 AA013641NIH HHS P51 OD011092
6 · The paper itself

Abstract

Alterations in DNA methylation have been associated with alcohol exposure and proposed to contribute to continued alcohol use; however, the molecular mechanisms involved remain obscure. We investigated the escalating effects of alcohol use on DNA methylation, gene expression and predicted neural effects in the nucleus accumbens of rhesus macaques that self-administered 4% alcohol for over 12 months. Using an exploratory approach to identify CpG-rich regions, followed by bisulfite sequencing, the methylation levels of 2.7 million CpGs were compared between seven low-binge drinkers and nine heavy-very heavy drinking subjects. We identified 17 significant differential methylation regions (DMRs), including 14 with methylation levels that were correlated with average daily alcohol consumption. The size of the DMRs ranged from 29 to 158 bp (mean=63.7), included 4-19 CpGs per DMR (mean=8.06) and spanned a range of average methylation values from 5 to 34%. Eight of the DMRs mapped to genes implicated in modulating synaptic plasticity. Six of the synaptic genes have not previously been linked to alcohol use. Validation studies of these eight DMRs using bisulfite amplicon sequencing and an expanded set of 30 subjects confirmed the significant alcohol-dose-associated methylation of the DMRs. Expression analysis of three of the DMR-associated genes, LRP5, GPR39 and JAKMIP1, revealed significant correlations between DMR methylation and whole-gene or alternative transcript expression, supporting a functional role in regulating gene expression. Together, these studies suggest that alcohol-associated synaptic remodeling may be regulated and coordinated at the level of DNA methylation.

Indexed as

AlcoholismAnimalsBinge DrinkingCase-Control StudiesCentral Nervous System DepressantsCpG IslandsDNA MethylationDose-Response Relationship, DrugEthanolGene Expression RegulationHigh-Throughput Nucleotide SequencingHumansMacaca mulattaMaleNucleus AccumbensReal-Time Polymerase Chain ReactionCentral Nervous System DepressantsEthanol

Identifiers

PMID28072409
PMCPMC5545731
OpenAlexW2568765397

What OpenQuestion holds

Textmetadata
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.