Evidence map›Paper›PMID 42103735›Full record

SynthesisTranslational psychiatry2026

Identifying novel gene dysregulation associated with opioid overdose death: a meta-analysis of differential gene expression in human prefrontal cortex.

Javan K Carter, Bryan C Quach, Caryn Willis, Melyssa S Minto, Dana B Hancock, Janitza Montalvo-Ortiz, Olivia Corradin, Ryan W Logan, Consuelo Walss-Bass, Brion S Maher and 2 more

Abstract readMeta-Analysis
In one paragraph

Synthesis in Translational psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Javan K CarterOmics, Epidemiology, and Analytics Program, RTI International, Research Triangle Park, Durham, NC, USA. jcarter@rti.org.
Bryan C QuachOmics, Epidemiology, and Analytics Program, RTI International, Research Triangle Park, Durham, NC, USA.ORCID http://orcid.org/0000-0002-1094-3104
Caryn WillisOmics, Epidemiology, and Analytics Program, RTI International, Research Triangle Park, Durham, NC, USA.
Melyssa S MintoOmics, Epidemiology, and Analytics Program, RTI International, Research Triangle Park, Durham, NC, USA.ORCID http://orcid.org/0000-0002-5438-7285
Dana B HancockOmics, Epidemiology, and Analytics Program, RTI International, Research Triangle Park, Durham, NC, USA.ORCID http://orcid.org/0000-0003-2240-3604
Janitza Montalvo-OrtizDepartment of Psychiatry, Division of Human Genetics, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-7657-8365
Olivia CorradinWhitehead Institute Biomedical Research, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-9484-0873
Ryan W LoganDepartment of Psychiatry, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0001-8579-015X
Consuelo Walss-BassLouis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Brion S MaherDepartment of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-9809-0064
PGC-SUD Epigenetics Working Group
Eric Otto JohnsonOmics, Epidemiology, and Analytics Program, RTI International, Research Triangle Park, Durham, NC, USA. ejohnson@rti.org.ORCID http://orcid.org/0000-0002-8870-1949

Funding

Synergy Core (SynC)P50DA054071 · NIDA · RESEARCH TRIANGLE INSTITUTE · PI Eric Otto Johnson · 2022 to 2026
$13.1M
NIDA NIH HHS P50 DA054071U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) DA043980U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) DA044859U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) DA050160U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) DA051390U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) DA05471
6 · The paper itself

Abstract

Only recently have human postmortem brain studies of differential gene expression (DGE) associated with opioid overdose death (OOD) been published; sample sizes from these studies have been modest (N = 40-153). To increase statistical power to identify OOD-associated genes, we leveraged human prefrontal cortex RNA-seq data from four independent OOD studies and conducted a transcriptome-wide DGE meta-analysis (N = 272). Using a unified gene expression data processing and analysis framework across studies, we meta-analyzed 20, 098 genes and found 335 significant differentially expressed genes (DEGs) by OOD status (false discovery rate < 0.05). Of these, 66 DEGs were among the list of 303 genes reported as OOD-associated in prior prefrontal cortex molecular studies (e.g., genes/gene families OPRK1, NPAS4, DUSP, EGR). The remaining 269 DEGs were not previously reported (e.g., NR4A2, SYT1, HCRTR2, BDNF). There was little evidence of genetic drivers for the observed differences in gene expression between opioid addiction cases and controls. Enrichment analyses for the DEGs across molecular pathway and biological process databases highlight an interconnected set of genes and pathways linked to orexin and tyrosine kinase receptors through MEK/ERK/MAPK signaling to affect neuronal plasticity.

Indexed as

Gene Expression RegulationOpiate OverdosePrefrontal CortexGene Expression ProfilingHumansTranscriptome

Identifiers

PMID42103735
PMCPMC13338397

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.