Document Type
Article
Publication Date
10-15-2024
Original Citation
Johnson E,
Fisher H,
Sullivan K,
Corradin O,
Sanchez-Roige S,
Gaddis N,
Sami Y,
Townsend A,
Teixeira Prates E,
Pavicic M,
Kruse P,
Chesler E,
Palmer A,
Troiani V,
Bubier JA,
Jacobson D,
Maher B.
An emerging multi-omic understanding of the genetics of opioid addiction. J Clin Invest. 2024;134(20):e172886.
Keywords
JMG, Humans, Opioid-Related Disorders, Genome-Wide Association Study, Animals, Receptors, Opioid, mu, Brain, Multiomics
JAX Source
J Clin Invest. 2024;134(20):e172886.
ISSN
1558-8238
PMID
39403933
DOI
https://doi.org/10.1172/jci172886
Grant
This work was funded by National Institute on Drug Abuse grants DA054071 (to EOJ, AAP, BSM, DAJ, EJC, JAB, NCG, OC, SSR, VT) and DA051913 (to EOJ and DAJ). This manuscript has been coauthored by employees of UT-Battelle LLC (JAB, KAS, AT, ETP, MP, PK), under contract no. DE-AC05-00OR22725 with the US Department of Energy.
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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.