期刊
SCIENTIFIC REPORTS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-019-41110-7
关键词
-
资金
- National Institutes of Health [R01 DA12690, R01 AA11330, 5T32 MH14276, P50 AA12870]
- Biological Sciences Training Program [5T32 MH14276]
- NARSAD Young Investigator Grant
- NIH GEI [U01HG004438]
- National Institute on Alcohol Abuse and Alcoholism
- National Institute on Drug Abuse
- NIH [HHSN268200782096C]
There is currently an epidemic of opioid use, overdose, and dependence in the United States. Although opioid dependence (OD) is more prevalent in men, opioid relapse and fatal opioid overdoses have recently increased at a higher rate among women. Epigenetic mechanisms have been implicated in the etiology of OD, though most studies to date have used candidate gene approaches. We conducted the first epigenome-wide association study (EWAS) of OD in a sample of 220 European-American (EA) women (140 OD cases, 80 opioid-exposed controls). DNA was derived from whole blood samples and EWAS was implemented using the Illumina Infinium HumanMethylationEPIC array. To identify differentially methylated CpG sites, we performed an association analysis adjusting for age, estimates of cell proportions, smoking status, and the first three principal components to correct for population stratification. After correction for multiple testing, association analysis identified three genome-wide significant differentially methylated CpG sites mapping to the PARG, RERE, and CFAP77 genes. These genes are involved in chromatin remodeling, DNA binding, cell survival, and cell projection. Previous genome-wide association studies have identified RERE risk variants in association with psychiatric disorders and educational attainment. DNA methylation age in the peripheral blood did not differ between OD subjects and opioid-exposed controls. Our findings implicate epigenetic mechanisms in OD and, if replicated, identify possible novel peripheral biomarkers of OD that could inform the prevention and treatment of the disorder.
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