Integrating Genetic and Gene Co-expression Analysis Identifies Gene Networks Involved in Alcohol and Stress Responses

文献类型： 外文期刊

第一作者： Luo, Jie

作者： Luo, Jie;Xu, Shengchun;Wang, Gangjun;Luo, Jie;Lv, Xiaonan;Xu, Pei;Wan, Hongjian;Xu, Pei;Cao, Peijian;Cook, Melloni N.;Jones, Byron C.;Lu, Lu;Cook, Melloni N.;Lu, Lu;Wang, Xusheng

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关键词： alcohol; stress; network analysis; transcriptome; BXD mice strains; causality analysis

期刊名称：FRONTIERS IN MOLECULAR NEUROSCIENCE （ 影响因子：5.639； 五年影响因子：5.76 ）

ISSN： 1662-5099

年卷期： 2018 年 11 卷

页码：

收录情况： SCI

摘要： Although the link between stress and alcohol is well recognized, the underlying mechanisms of how they interplay at the molecular level remain unclear. The purpose of this study is to identify molecular networks underlying the effects of alcohol and stress responses, as well as their interaction on anxiety behaviors in the hippocampus of mice using a systems genetics approach. Here, we applied a gene co-expression network approach to transcriptomes of 41 BXD mouse strains under four conditions: stress, alcohol, stress-induced alcohol and control. The co-expression analysis identified 14 modules and characterized four expression patterns across the four conditions. The four expression patterns include up-regulation in no restraint stress and given an ethanol injection (NOE) but restoration in restraint stress followed by an ethanol injection (RSE; pattern 1), down-regulation in NOE but rescue in RSE (pattern 2), up-regulation in both restraint stress followed by a saline injection (RSS) and NOE, and further amplification in RSE (pattern 3), and up-regulation in RSS but reduction in both NOE and RSE (pattern 4). We further identified four functional subnetworks by superimposing protein-protein interactions (PPIs) to the 14 co-expression modules, including gamma-aminobutyric acid receptor (GABA) signaling, glutamate signaling, neuropeptide signaling, cAMP-dependent signaling. We further performed module specificity analysis to identify modules that are specific to stress, alcohol, or stress-induced alcohol responses. Finally, we conducted causality analysis to link genetic variation to these identified modules, and anxiety behaviors after stress and alcohol treatments. This study underscores the importance of integrative analysis and offers new insights into the molecular networks underlying stress and alcohol responses.

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