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

Author:

Lee Mikyeong1ORCID,Joehanes Roby2ORCID,McCartney Daniel L3,Kho Minjung4,Hüls Anke5,Wyss Annah B1,Liu Chunyu67,Walker Rosie M89,R Kardia Sharon L4,Wingo Thomas S10,Burkholder Adam11,Ma Jiantao2,Campbell Archie3,Wingo Aliza P12,Huan Tianxiao213,Sikdar Sinjini114,Keshawarz Amena1516,Bennett David A17,Smith Jennifer A4,Evans Kathryn L3,Levy Daniel2,London Stephanie J1ORCID

Affiliation:

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.

Publisher

Future Medicine Ltd

Subject

Cancer Research,Genetics

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