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

Mikyeong Lee; Roby Joehanes; Daniel L McCartney; Minjung Kho; Anke Hüls; Annah B Wyss; Chunyu Liu; Rosie M Walker; Sharon L R Kardia; Thomas S Wingo; Adam Burkholder; Jiantao Ma; Archie Campbell; Aliza P Wingo; Tianxiao Huan; Sinjini Sikdar; Amena Keshawarz; David A Bennett; Jennifer A Smith; Kathryn L Evans; Daniel Levy; Stephanie J London

doi:10.2217/epi-2022-0353

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.

Authors

Mikyeong Lee¹, Roby Joehanes², Daniel L McCartney³, Minjung Kho⁴, Anke Hüls⁵, Annah B Wyss¹, Chunyu Liu^{6

7}, Rosie M Walker^{8

9}, Sharon L R Kardia⁴, Thomas S Wingo¹⁰, Adam Burkholder¹¹, Jiantao Ma², Archie Campbell³, Aliza P Wingo¹², Tianxiao Huan^{2

13}, Sinjini Sikdar^{1

14}, Amena Keshawarz^{15

16}, David A Bennett¹⁷, Jennifer A Smith⁴, Kathryn L Evans³, Daniel Levy², Stephanie J London¹

Affiliations

¹ Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
² Department of Health and Human Services, Framingham Heart Study, National Heart, Lung, and Blood Institute, National Institutes of Health, Framingham, MA 01702, USA.
³ Centre for Genomic & Experimental Medicine, Institute of Genetics & Cancer, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, UK.
⁴ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
⁵ Department of Epidemiology & Gangarosa, Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
⁶ Department of Biostatistics, School of Public Health, Boston University, Boston, MA 02215, USA.
⁷ Framingham Heart Study, Boston University, Framingham, MA 01702, USA.
⁸ Centre for Clinical Brain Science, Chancellor's Building, 49 Little France Crescent, Edinburgh Bioquarter, Edinburgh, UK.
⁹ School of Psychology, University of Exeter, Exeter, UK.
¹⁰ Department of Neurology & Human Genetics, Emory University, Atlanta, GA 30322, USA.
¹¹ Office of Environmental Science Cyberinfrastructure, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
¹² Department of Psychiatry & Behavioral Sciences, Emory University, Atlanta, GA 30322, USA.
¹³ Department of Ophthalmology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
¹⁴ Department of Mathematics & Statistics, Old Dominion University, Norfolk, VA 23529, USA.
¹⁵ Framingham Heart Study, Framingham, MA 01702, USA.
¹⁶ Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
¹⁷ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA.

Abstract

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

Substances

Analgesics, Opioid

Abstract

Publication types

MeSH terms

Substances

Grants and funding