Multiomic Network Analysis Identifies Dysregulated Neurobiological Pathways in Opioid Addiction.
Document Type
Article
Publication Date
7-1-2025
Original Citation
Sullivan K,
Kainer D,
Lane M,
Cashman M,
Miller J,
Garvin M,
Townsend A,
Quach B,
Willis C,
Kruse P,
Gaddis N,
Mathur R,
Corradin O,
Maher B,
Scacheri P,
Sanchez-Roige S,
Palmer A,
Troiani V,
Chesler E,
Kember R,
Kranzler H,
Justice A,
Xu K,
Aouizerat B,
Hancock D,
Johnson E,
Jacobson D,
.
Multiomic Network Analysis Identifies Dysregulated Neurobiological Pathways in Opioid Addiction. Biol Psychiatry. 2025;98(1):11-22.
Keywords
JMG, Humans, Opioid-Related Disorders, Genome-Wide Association Study, Machine Learning, Prefrontal Cortex, Proteomics, Brain-Derived Neurotrophic Factor, Transcriptome, Opiate Overdose, Systems Biology, Signal Transduction, Gene Regulatory Networks
JAX Source
Biol Psychiatry. 2025;98(1):11-22.
ISSN
1873-2402
PMID
39615775
DOI
https://doi.org/10.1016/j.biopsych.2024.11.013
Abstract
BACKGROUND: Opioid 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.
METHODS: To 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.
RESULTS: We 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.
CONCLUSIONS: Our 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.