An emerging multi-omic understanding of the genetics of opioid addiction
Name
172886.1-20241011165600-covered-4fa089109ce452e764bbb8648b44a723.pdf
Description
Published version
Size
817.69 KB
Format
Adobe PDF
Checksum (MD5)
9c5ae6d3bcced79d7b1b0981270ae8de
Author(s)
Johnson, Eric O
Fisher, Heidi S
Sullivan, Kyle A
Corradin, Olivia
Sanchez-Roige, Sandra
Gaddis, Nathan C
Sami, Yasmine N
Townsend, Alice
Teixeira Prates, Erica
Pavicic, Mirko
Date Issued
October 15, 2024
Journal
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Version
Final published version
Abstract
Opioid misuse, addiction, and associated overdose deaths remain global public health crises. Despite the tremendous need for pharmacological treatments, current options are limited in number, use, and effectiveness. Fundamental leaps forward in our understanding of the biology driving opioid addiction are needed to guide development of more effective medication-assisted therapies. This Review focuses on the omics-identified biological features associated with opioid addiction. Recent GWAS have begun to identify robust genetic associations, including variants in OPRM1, FURIN, and the gene cluster SCAI/PPP6C/RABEPK. An increasing number of omics studies of postmortem human brain tissue examining biological features (e.g., histone modification and gene expression) across different brain regions have identified broad gene dysregulation associated with overdose death among opioid misusers. Drawn together by meta-analysis and multi-omic systems biology, and informed by model organism studies, key biological pathways enriched for opioid addiction-associated genes are emerging, which include specific receptors (e.g., GABAB receptors, GPCR, and Trk) linked to signaling pathways (e.g., Trk, ERK/MAPK, orexin) that are associated with synaptic plasticity and neuronal signaling. Studies leveraging the agnostic discovery power of omics and placing it within the context of functional neurobiology will propel us toward much-needed, field-changing breakthroughs, including identification of actionable targets for drug development to treat this devastating brain disease.
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DOI of Published Version
https://doi.org/10.1172/jci172886
