Genetics and Epigenetics of Substance Use

Vanyukov, Michael; Tarter, Ralph E.

doi:10.1007/978-3-030-00627-3_4

Cited by 7 publications

(2 citation statements)

References 84 publications

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“…Epigenetic changes have emerged as a leading potential biological marker of drug dependence given their implications for transcription regulation and cellular reprogramming (3). Among these changes, DNA methylation (DNAm) at cytosine-guanine (CpG) sites has received the most attention in substance use research (4). Studies in animal models provide robust evidence that substance abuse causes changes in gene expression through changes in DNAm (5).…”

Section: Introductionmentioning

confidence: 99%

Epigenome-Wide Study of Brain DNA Methylation Among Opioid Users and Controls

Shu

Sosnowski

Tao

et al. 2020

Preprint

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Opioid abuse poses significant risk to individuals in the United States and epigenetic changes are a leading potential biomarker of abuse. Current evidence, however, is mostly limited to candidate gene analysis in whole blood. To clarify the association between opioid abuse and DNA methylation, we conducted an epigenome-wide analysis (EWAS) of DNA methylation in brains of individuals who died from opioid intoxication and controls. Tissue samples were extracted from the dorsolateral prefrontal cortex of 160 deceased individuals (Mage = 35.15, SD = 9.42 years; 62% male; 78% White). The samples included 73 individuals who died of opioid intoxication, 59 group-matched psychiatric controls, and 28 group-matched normal controls. EWAS was implemented using the Illumina Infinium MethylationEPIC BeadChip; analyses adjusted for sociodemographic characteristics, negative control and ancestry principal components, cellular composition, and surrogate variables. Epigenetic age was calculated using the Horvath and Levine clocks, and gene ontology (GO) analyses were performed. No CpG sites were epigenome-wide significant after multiple testing correction, but 13 sites reached nominal significance (p < 1.0 x 10-5). There was a significant association between opioid use and Levine phenotypic age (b = 2.24, se = 1.11, p = .045). Opioid users were approximately two years phenotypically older compared to controls. GO analyses revealed enriched pathways related to cell function and neuron differentiation, but no terms survived multiple testing correction. Results inform our understanding of the neurobiology of opioid use, and future research with larger samples across stages of opioid use will elucidate the complex genomics of opioid abuse.

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Section: Introductionmentioning

confidence: 99%

Epigenome-Wide Study of Brain DNA Methylation Among Opioid Users and Controls

Shu

Sosnowski

Tao

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Namely, as extensively reviewed previously [8,17,18], the various patterns of initiation, polydrug use, as well as the development of addiction, are readily accounted for by the parsimonious construct of common liability to drug use/addiction (CLA). This position is grounded in the long-standing human genetics concept [19] and the abundant data on common mechanisms of drug response and behaviour regulation.…”

mentioning

confidence: 99%