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Genome-Wide Correlation of DNA Methylation and Gene Expression in Postmortem Brain Tissues of Opioid Use Disorder Patients.


ABSTRACT:

Background

Opioid use disorder (OUD) affects millions of people, causing nearly 50 000 deaths annually in the United States. While opioid exposure and OUD are known to cause widespread transcriptomic and epigenetic changes, few studies in human samples have been conducted. Understanding how OUD affects the brain at the molecular level could help decipher disease pathogenesis and shed light on OUD treatment.

Methods

We generated genome-wide transcriptomic and DNA methylation profiles of 22 OUD subjects and 19 non-psychiatric controls. We applied weighted gene co-expression network analysis to identify genetic markers consistently associated with OUD at both transcriptomic and methylomic levels. We then performed functional enrichment for biological interpretation. We employed cross-omics analysis to uncover OUD-specific regulatory networks.

Results

We found 6 OUD-associated co-expression gene modules and 6 co-methylation modules (false discovery rate <0.1). Genes in these modules are involved in astrocyte and glial cell differentiation, gliogenesis, response to organic substance, and response to cytokine (false discovery rate <0.05). Cross-omics analysis revealed immune-related transcription regulators, suggesting the role of transcription factor-targeted regulatory networks in OUD pathogenesis.

Conclusions

Our integrative analysis of multi-omics data in OUD postmortem brain samples suggested complex gene regulatory mechanisms involved in OUD-associated expression patterns. Candidate genes and their upstream regulators revealed in astrocyte, and glial cells could provide new insights into OUD treatment development.

SUBMITTER: Liu A 

PROVIDER: S-EPMC8598308 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Genome-Wide Correlation of DNA Methylation and Gene Expression in Postmortem Brain Tissues of Opioid Use Disorder Patients.

Liu Andi A   Dai Yulin Y   Mendez Emily F EF   Hu Ruifeng R   Fries Gabriel R GR   Najera Katherine E KE   Jiang Shan S   Meyer Thomas D TD   Stertz Laura L   Jia Peilin P   Walss-Bass Consuelo C   Zhao Zhongming Z  

The international journal of neuropsychopharmacology 20211101 11


<h4>Background</h4>Opioid use disorder (OUD) affects millions of people, causing nearly 50 000 deaths annually in the United States. While opioid exposure and OUD are known to cause widespread transcriptomic and epigenetic changes, few studies in human samples have been conducted. Understanding how OUD affects the brain at the molecular level could help decipher disease pathogenesis and shed light on OUD treatment.<h4>Methods</h4>We generated genome-wide transcriptomic and DNA methylation profil  ...[more]

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