Evidence map›Paper›PMID 39615775›Full record

ArticleBiological psychiatry2025

Multiomic Network Analysis Identifies Dysregulated Neurobiological Pathways in Opioid Addiction.

Kyle A Sullivan, David Kainer, Matthew Lane, Mikaela Cashman, J Izaak Miller, Michael R Garvin, Alice Townsend, Bryan C Quach, Caryn Willis, Peter Kruse and 18 more

Abstract read
In one paragraph

Article in Biological psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

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

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. 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

28 authors.

Kyle A SullivanBiosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee.
David KainerBiosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee.
Matthew LaneThe Bredesen Center for Interdisciplinary Research and Graduate Education, University of Tennessee-Knoxville, Knoxville, Tennessee.
Mikaela CashmanBiosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee; Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, California.
J Izaak MillerBiosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee.
Michael R GarvinBiosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee.
Alice TownsendThe Bredesen Center for Interdisciplinary Research and Graduate Education, University of Tennessee-Knoxville, Knoxville, Tennessee.
Bryan C QuachRTI International, Research Triangle Park, North Carolina.
Caryn WillisRTI International, Research Triangle Park, North Carolina.
Peter KruseThe Bredesen Center for Interdisciplinary Research and Graduate Education, University of Tennessee-Knoxville, Knoxville, Tennessee.
Nathan C GaddisRTI International, Research Triangle Park, North Carolina.
Ravi MathurRTI International, Research Triangle Park, North Carolina.
Olivia CorradinWhitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Brion S MaherDepartment of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Peter C ScacheriDepartment of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio.
Sandra Sanchez-RoigeDepartment of Psychiatry, University of California San Diego, La Jolla, California; Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Abraham A PalmerDepartment of Psychiatry, University of California San Diego, La Jolla, California; Institute for Genomic Medicine, University of California San Diego, La Jolla, California.
Vanessa TroianiGeisinger College of Health Sciences, Scranton, Pennsylvania.
Elissa J CheslerThe Jackson Laboratory, Bar Harbor, Maine.
Rachel L KemberMental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania; Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Henry R KranzlerMental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania; Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Amy C JusticeVeterans Affairs Connecticut Healthcare System, West Haven, Connecticut; Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut; Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut.
Ke XuVeterans Affairs Connecticut Healthcare System, West Haven, Connecticut; Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut.
Bradley E AouizeratBluestone Center for Clinical Research, College of Dentistry, New York University, New York, New York.
Dana B HancockRTI International, Research Triangle Park, North Carolina. Electronic address: dhancock@rti.org.
Eric O JohnsonRTI International, Research Triangle Park, North Carolina; Fellow Program, RTI International, Research Triangle Park, North Carolina. Electronic address: ejohnson@rti.org.
Daniel A JacobsonBiosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee. Electronic address: jacobsonda@ornl.gov.
VA Million Veteran Program

Funding

Synergy Core (SynC)P50DA054071 · NIDA · RESEARCH TRIANGLE INSTITUTE · PI Daniel A Jacobson · 2022 to 2026
$13.1M
Radiochemistry CoreP30DA046345 · NIDA · UNIVERSITY OF PENNSYLVANIA · PI MACH, ROBERT H · 2019 to 2023
$9.4M
Gene Network Identification and Integration (GNetii) Approach to Understanding the Biology Underlying HIV and Drug Abuse.R01DA051908 · NIDA · RESEARCH TRIANGLE INSTITUTE · PI JACOBSON, DANIEL A, JOHNSON, ERIC OTTO · 2020 to 2024
$3.4M
Feature selection of DNA methylation biosignatures for neuropathy with comorbid drug abuse in the setting of HIV infectionR01DA047820 · NIDA · YALE UNIVERSITY · PI AOUIZERAT, BRADLEY E, XU, KE · 2018 to 2022
$2.9M
Integrating Multiple Omics to Illuminate Gene Networks Underlying Cigarette Smoking and Opioids.R01DA051913 · NIDA · RESEARCH TRIANGLE INSTITUTE · PI HANCOCK, DANA B, JACOBSON, DANIEL A · 2020 to 2024
$2.9M
Defining the impact of injection drug use on antiretroviral therapy and HIV treatment outcomes: an (epi)genomic approachR01DA047063 · NIDA · YALE UNIVERSITY · PI AOUIZERAT, BRADLEY E, XU, KE · 2018 to 2022
$2.4M
BLRD VA I01 BX004820NIDA NIH HHS P30 DA046345NIDA NIH HHS P50 DA054071NIDA NIH HHS R01 DA047063NIDA NIH HHS R01 DA047820NIDA NIH HHS R01 DA051908NIDA NIH HHS R01 DA051913
6 · The paper itself

Abstract

backgroundOpioid addiction is a worldwide public health crisis. In the United States, for example, opioids cause more drug overdose deaths than any other substance. However, opioid addiction treatments have limited efficacy, meaning that additional treatments are needed.

methodsTo help address this problem, we used network-based machine learning techniques to integrate results from genome-wide association studies of opioid use disorder and problematic prescription opioid misuse with transcriptomic, proteomic, and epigenetic data from the dorsolateral prefrontal cortex of people who died of opioid overdose and control individuals.

resultsWe identified 211 highly interrelated genes identified by genome-wide association studies or dysregulation in the dorsolateral prefrontal cortex of people who died of opioid overdose that implicated the Akt, BDNF (brain-derived neurotrophic factor), and ERK (extracellular signal-regulated kinase) pathways, identifying 414 drugs targeting 48 of these opioid addiction-associated genes. Some of the identified drugs are approved to treat other substance use disorders or depression.

conclusionsOur synthesis of multiomics using a systems biology approach revealed key gene targets that could contribute to drug repurposing, genetics-informed addiction treatment, and future discovery.

Indexed as

Opioid-Related DisordersPrefrontal CortexBrain-Derived Neurotrophic FactorGene Regulatory NetworksGenome-Wide Association StudyHumansMachine LearningOpiate OverdoseProteomicsSignal TransductionSystems BiologyTranscriptomeBrain-Derived Neurotrophic FactorAddictionBioinformaticsMultiomicNetworksOpioidsSystems biology

Identifiers

PMID39615775
PMCPMC12119972

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.