Potential Targets For Opioid Addiction Treatment Uncovered By GWAS

Pixabay License | Source: Arek Socha, no changes made.
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The USA is in the midst of an opioid addiction crisis with overdoses having killed 47,600 people in 2017, according to the Centers for Disease Control and Prevention (CDC). Opioids such as OxyContin® and Vicodin® are used in pain medications and many Americans are addicted to their meds with figures indicating that 2.6 million people suffer from opioid use disorder.

As well as alternatives to opioid pain medications, medications that can help relieve existing addictions are needed. A new genome-wide association study (GWAS) published in the Journal of Clinical Medicine with senior author Lindsay A. Farrer, PhD, Professor of biostatistics at the Boston University School of Medicine, has for the first time suggested that several genes as well as the vitamin D metabolism and fibroblast growth factor (FGF) signaling pathways may be associated with opioid cessation, indicating potential therapeutic targets. New addiction treatments and finding ways to increase the uptake of those treatments are needed as only 7% of people with opioid use disorder receive medications, and only 20% receive any form of treatment.

Due to limited datasets on opioid use cessation, multinational sources were needed, found in the United States, Australia, with additional exploration using the UK Biobank. No single nucleotide polymorphisms (SNPs) were found to be associated with cessation using the accepted genome-wide significance level of p < 5 × 10-8, however nine independent regions were identified using a p < 1 × 10−5 cut-off. The authors considered the locations of three of the SNPs to be biologically relevant, those in protein tyrosine phosphatase (PTP) family member PTPRD, cardiac and skeletal muscle expressed MYOM2, and the long non-coding RNA (lncRNA) SNAP25-AS1 which targets a t-SNARE involved in neurotransmitter release.

Enriched genetic variation in the vitamin D metabolism pathway and fibroblast growth factor (FGF) signaling pathway was found. The authors hypothesize that more efficient vitamin D metabolism may lead to greater physical fitness aiding the cessation of opioid use. The FGF pathway was previously associated with morphine tolerance. Furthermore, there is cross-talk between FGF and vitamin D, with FGF23 reducing the levels of activated vitamin D.

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Polygenic risk score associations with opioid cessation were found in being a former drinker, former smoker and with back pain persistent for more than three months using the UK biobank dataset.

Limitations of the study include statistical non-significance of the associations and the fact that opioid cessation was self-reported and not followed up in the long-term. The datasets only contained people of African and European ancestry.

“Despite an absence of genome-wide significant variants for opioid cessation, these results provide evidence for genetic influences on opioid cessation, suggest genetic overlap with other relevant traits, and may indicate potential novel therapeutic targets for [opioid use disorder]”, concluded the authors.

Sources

  1. https://www.cdc.gov/drugoverdose/data/statedeaths.html
  2. https://ukhealthcare.uky.edu/blog/post/-promising-results-in-uk-clinical-trial-get-opioid-therapy-closer-to-market
  3. https://www.research.uky.edu/news/uk-awarded-3-million-study-influences-using-opioid-medications-criminal-justice-setting
  4. https://www.drugabuse.gov/publications/misuse-prescription-drugs/overview
  5. https://www.mdpi.com/2077-0383/9/1/180