Genome-Wide Correlation of DNA Methylation and Gene Expression in Postmortem Brain Tissues of Opioid Use Disorder Patients.
Genome-Wide Correlation of DNA Methylation and Gene Expression in Postmortem Brain Tissues of Opioid Use Disorder Patients.
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DOI：
10.1093/ijnp/pyab043
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发表时间：
2021-11-12
期刊：
影响因子：
--
通讯作者：
Zhao Z
中科院分区：
文献类型：
--
作者：
Liu A;Dai Y;Mendez EF;Hu R;Fries GR;Najera KE;Jiang S;Meyer TD;Stertz L;Jia P;Walss-Bass C;Zhao Z
阿片类药物使用障碍（OUD）影响着数百万人，在美国每年造成近5万人死亡。虽然已知阿片类药物暴露和OUD会引起广泛的转录组学和表观遗传变化，但在人类样本中进行的研究很少。了解OUD如何在分子水平上影响大脑，有助于破译疾病的发病机制，并阐明OUD的治疗方法。我们生成了22名OUD受试者和19名非精神病对照的全基因组转录组学和DNA甲基化谱。我们应用加权基因共表达网络分析来确定在转录组和甲基组水平上与OUD一致相关的遗传标记。然后我们进行了功能富集以进行生物学解释。我们采用交叉组学分析来揭示oud特异性调控网络。我们发现了6个与oud相关的共表达基因模块和6个共甲基化模块（错误发现率<0.1）。这些模块中的基因参与星形胶质细胞和胶质细胞的分化、胶质形成、对有机物质的反应和对细胞因子的反应（错误发现率<0.05）。交叉组学分析揭示了免疫相关的转录调节因子，提示转录因子靶向调节网络在OUD发病机制中的作用。我们对OUD死后脑样本的多组学数据进行了综合分析，表明OUD相关表达模式涉及复杂的基因调控机制。星形胶质细胞和神经胶质细胞中发现的候选基因及其上游调控因子可能为OUD治疗的发展提供新的见解。
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. 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. 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. 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.
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WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
6.8
作者：
Cecil CA;Walton E;Smith RG;Viding E;McCrory EJ;Relton CL;Suderman M;Pingault JB;McArdle W;Gaunt TR;Mill J;Barker ED
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Barker ED
影响因子：
9.3
作者：
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通讯作者：
Alexander GC
影响因子：
5.9
作者：
Crist RC;Reiner BC;Berrettini WH
通讯作者：
Berrettini WH
影响因子：
--
作者：
Merikangas, KR;Stolar, M;Rounsaville, BJ
通讯作者：
Rounsaville, BJ