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

Shu, Chang; Sosnowski, David W.; Tao, Ran; Deep-Soboslay, Amy; Kleinman, Joel E.; Hyde, Thomas M.; Jaffe, Andrew E.; Sabunciyan, Sarven; Maher, Brion S.

doi:10.1101/2020.11.10.377069

Cited by 4 publications

(7 citation statements)

References 34 publications

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“…In addition, a CpG site in the promoter region of human Mab21l2 (cg05878390 in the 450k array) was among the top 20 significant differentially methylated CpGs associated with age in a fetal lung dataset of in-utero-smoke and control samples at 57-122 days of gestation 50 . This gene was also differentially methylated in the dorsolateral prefrontal cortex of opioid users in humans, and there was a significant association between opioid use and the Levine phenotypic age 51 . Thus, Mab21l2 emerges as a conserved gene involved in the epigenetic aging process.…”

Section: Discussionmentioning

confidence: 97%

Epigenetic aging of the demographically non-aging naked mole-rat

et al. 2022

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The naked mole-rat (NMR) is an exceptionally long-lived rodent that shows no increase of mortality with age, defining it as a demographically non-aging mammal. Here, we perform bisulfite sequencing of the blood of > 100 NMRs, assessing > 3 million common CpG sites. Unsupervised clustering based on sites whose methylation correlates with age reveals an age-related methylome remodeling, and we also observe a methylome information loss, suggesting that NMRs age. We develop an epigenetic aging clock that accurately predicts the NMR age. We show that these animals age much slower than mice and much faster than humans, consistent with their known maximum lifespans. Interestingly, patterns of age-related changes of clock sites in Tert and Prpf19 differ between NMRs and mice, but there are also sites conserved between the two species. Together, the data indicate that NMRs, like other mammals, epigenetically age even in the absence of demographic aging of this species.

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Section: Discussionmentioning

confidence: 97%

Epigenetic aging of the demographically non-aging naked mole-rat

et al. 2022

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“…2B). Not surprisingly, a large majority focused on the mesocorticolimbic dopaminergic pathway: the NAc (21 articles [8,22,26,[28][29][30]32,[40][41][42][43][44][45][46][47][48][49][50][51][52][53]), frontal cortex (13 articles [8,25,27,29,51,[54][55][56][57][58][59][60][61]), whole/unspecified striatal complex (11 articles [24,33,[62][63][64][65][66][67][68][69][70]), dorsal striatum (7 articles [8,30,[48][49]…”

Section: Route and Duration Of Opioid Administrationmentioning

confidence: 99%

“…While the first RNA-seq study was published in 2014 12 , this technique has since progressively replaced microarrays, reflecting its well-recognized advantages (higher sensitivity and throughput, potential for gene discovery). For epigenomic profiling, 3 studies recently performed bisulfite sequencing [51,59,61], and only 1 used ATACseq (Assay for Transposase-Accessible Chromatin with sequencing) [72]. Considering rapid improvements in throughput and resolution of sequencing methodologies (see below), these trends are expected to strengthen.…”

Section: Route and Duration Of Opioid Administrationmentioning

confidence: 99%

“…Regarding the epigenome, 2 recent studies (1 in the rat [51], 2 in humans [126,127]) investigated DNA methylation, a mark increasingly implicated in psychiatric pathophysiology [128]. The rat study used Whole Genome Bisulfite Sequencing (WGBS) to analyze DNA methylation changes during heroin IVSA, in a standard or enriched environment, in 3 brain regions (VTA, NAc and medial prefrontal cortex) [51].…”

Section: Non-coding and Epigenomic Mechanisms Of Opioid Plasticitymentioning

confidence: 99%

“…Also, because epigenetic landscapes determine cellular identity, differences observed in bulk tissue may reflect variations in cellular composition (which may contribute to pathogenesis), rather than transcriptional regulation. The second human study started to address these questions [126]. Using EPIC arrays to analyze bulk tissue, the authors adjusted for socio-demographic characteristics, ancestry and cellular composition.…”

Section: Non-coding and Epigenomic Mechanisms Of Opioid Plasticitymentioning

confidence: 99%

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Functional genomic mechanisms of opioid action and opioid use disorder: a systematic review of animal models and human studies

Falconnier

Caparros-Roissard

Decraene

et al. 2022

Preprint

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In the past two decades, over-prescription of opioids for pain management has driven a steep increase in opioid use disorder (OUD) and death by overdose, exerting a dramatic toll on western countries. OUD is a chronic relapsing disease associated with a lifetime struggle to control drug consumption, suggesting that opioids trigger long-lasting brain adaptations, notably through functional genomic and epigenomic mechanisms. Current understanding of these processes, however, remain scarce, and have not been previously reviewed systematically. To do so, the goal of the present work was to synthesize current knowledge on genome-wide transcriptomic and epigenetic mechanisms of opioid action, in primate and rodent species. Using a prospectively registered methodology, comprehensive literature searches were completed in PubMed, Embase, and Web of Science. Of the 2705 articles identified, 69 met our inclusion criteria and were considered for qualitative analysis. Focusing on the 5 most studied nervous system structures (nucleus accumbens, frontal cortex, whole striatum, dorsal striatum, spinal cord; 44 articles), we also conducted a quantitative analysis of differentially expressed genes, in an effort to identify a putative core transcriptional signature of opioids. Only one gene, Cdkn1a, was replicated in six studies and, globally, our results unveil surprisingly low consistency across published work, even when considering most recent single-cell approaches. Analysis of putative sources for this poor reproducibility suggest contributions from species, brain structures, duration of opioid exposure, as well as batch effects. To go beyond those limitations, we leveraged threshold-free methods to illustrate how genome-wide comparisons may generate new findings and hypotheses. Finally, we discuss current methodological development in the field, and their implication for future research and, ultimately, better care.

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