Opioid medication use and blood DNA methylation: epigenome-wide association meta-analysis

Epigenomics. 2022 Dec;14(23):1479-1492. doi: 10.2217/epi-2022-0353. Epub 2023 Jan 26.


Aim: To identify differential methylation related to prescribed opioid use. Methods: This study examined whether blood DNA methylation, measured using Illumina arrays, differs by recent opioid medication use in four population-based cohorts. We meta-analyzed results (282 users; 10,560 nonusers) using inverse-variance weighting. Results: Differential methylation (false discovery rate <0.05) was observed at six CpGs annotated to the following genes: KIAA0226, CPLX2, TDRP, RNF38, TTC23 and GPR179. Integrative epigenomic analyses linked implicated loci to regulatory elements in blood and/or brain. Additionally, 74 CpGs were differentially methylated in males or females. Methylation at significant CpGs correlated with gene expression in blood and/or brain. Conclusion: This study identified DNA methylation related to opioid medication use in general populations. The results could inform the development of blood methylation biomarkers of opioid use.

Keywords: blood; epigenetics; methylome; prescription opioids.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analgesics, Opioid*
  • CpG Islands
  • DNA Methylation*
  • Epigenesis, Genetic
  • Epigenome*
  • Female
  • Genome-Wide Association Study
  • Humans
  • Male


  • Analgesics, Opioid