Evidence map›Paper›PMID 33414398›Full record

ArticleTranslational psychiatry2021

Alcohol use disorder causes global changes in splicing in the human brain.

Derek Van Booven, Mengying Li, J Sunil Rao, Ilya O Blokhin, R Dayne Mayfield, Estelle Barbier, Markus Heilig, Claes Wahlestedt

Open access · goldAbstract read
In one paragraph

Article in Translational psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 8% 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

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Alternative splicing in addiction.Current opinion in genetics & development · 2025
    Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

8 authors at 3 institutions in 2 countries.

Derek Van BoovenJohn P. Hussman Institute of Human Genomics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
Mengying LiDepartment of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
J Sunil RaoDepartment of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
Ilya O BlokhinCenter for Therapeutic Innovation, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
R Dayne MayfieldWaggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX, 78712, USA.
Estelle BarbierCenter for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, S-581 85, Linköping, Sweden.
Markus HeiligCenter for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, S-581 85, Linköping, Sweden.ORCID 0000-0003-2706-2482
Claes WahlestedtCenter for Therapeutic Innovation, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. cwahlestedt@med.miami.edu.ORCID 0000-0003-4471-5916
University of Miami · USLinköping University · SEThe University of Texas at Austin · US

Funding

GENE EXPRESSION IN THE HUMAN ALCOHOLIC BRAINR01AA012404 · NIAAA · UNIVERSITY OF TEXAS AUSTIN · PI MAYFIELD, ROY DAYNE · 2000 to 2025
$10.7M
Brain Tissue Resource Centre for Alcohol ResearchR28AA012725 · NIAAA · UNIVERSITY OF SYDNEY · PI Greg Trevor Sutherland · 2012 to 2026
$7.0M
Next Generation Sequencing of Human Alcoholic BrainU01AA020926 · NIAAA · UNIVERSITY OF TEXAS AT AUSTIN · PI Roy DAYNE MAYFIELD · 2011 to 2026
$6.7M
Epigenetic Signaling Pathways Contributing to Alcohol DependenceR01AA023781 · NIAAA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI HEILIG, MARKUS ALEXANDER, WAHLESTEDT, CLAES ROBERT · 2015 to 2019
$2.1M
NIAAA NIH HHS R01 AA012404NIAAA NIH HHS R01 AA023781NIAAA NIH HHS R28 AA012725NIAAA NIH HHS U01 AA020926
6 · The paper itself

Abstract

Alcohol use disorder (AUD) is a widespread disease leading to the deterioration of cognitive and other functions. Mechanisms by which alcohol affects the brain are not fully elucidated. Splicing constitutes a nuclear process of RNA maturation, which results in the formation of the transcriptome. We tested the hypothesis as to whether AUD impairs splicing in the superior frontal cortex (SFC), nucleus accumbens (NA), basolateral amygdala (BLA), and central nucleus of the amygdala (CNA). To evaluate splicing, bam files from STAR alignments were indexed with samtools for use by rMATS software. Computational analysis of affected pathways was performed using Gene Ontology Consortium, Gene Set Enrichment Analysis, and LncRNA Ontology databases. Surprisingly, AUD was associated with limited changes in the transcriptome: expression of 23 genes was altered in SFC, 14 in NA, 102 in BLA, and 57 in CNA. However, strikingly, mis-splicing in AUD was profound: 1421 mis-splicing events were detected in SFC, 394 in NA, 1317 in BLA, and 469 in CNA. To determine the mechanism of mis-splicing, we analyzed the elements of the spliceosome: small nuclear RNAs (snRNAs) and splicing factors. While snRNAs were not affected by alcohol, expression of splicing factor heat shock protein family A (Hsp70) member 6 (HSPA6) was drastically increased in SFC, BLA, and CNA. Also, AUD was accompanied by aberrant expression of long noncoding RNAs (lncRNAs) related to splicing. In summary, alcohol is associated with genome-wide changes in splicing in multiple human brain regions, likely due to dysregulation of splicing factor(s) and/or altered expression of splicing-related lncRNAs.

Indexed as

AlcoholismRNA, Long NoncodingAlternative SplicingHumansNucleus AccumbensRNA SplicingRNA, Long Noncoding

Identifiers

PMID33414398
PMCPMC7790816
OpenAlexW3119278875

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.