DOI

https://doi.org/10.25772/076F-RX34

Defense Date

2020

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Integrative Life Sciences

First Advisor

Vladimir Vladimirov

Abstract

Alcohol use disorder (AUD) is a debilitating psychiatric illness that develops from a combination of genetic and environmental factors. While it is well documented that AUD is heritable, the shift from recreational alcohol use to abuse/dependence is poorly understood. In this dissertation, using postmortem brain tissue from individuals with alcohol dependence (AD), we profiled the genome-wide expression of circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) to better understand the impact of gene expression on the development of AUD. To achieve this, we performed two independent studies that explore transcriptome differences between AD cases and controls. The first of which examines differentially expressed gene (DEG) networks associated with AD that show either high or low levels of network preservation between two key areas of the mesocorticolimbic system (MCL), the prefrontal cortex (PFC) and nucleus accumbens (NAc). The second is a pilot study that interrogates the function of circRNA as miRNA sponges to impact the expression of mRNA. Overall, our findings corroborate results from recent studies while also providing novel evidence for biological processes that are differentially expressed between the PFC and NAc. Additionally, the second study is the first to explore circRNA:miRNA:mRNA interactions in the brains of chronic alcohol abusers and the role of circRNA as potential regulators of known AUD risk genes. Finally, we integrate genetic information in the form of eQTL analyses to determine the clinical relevance of these findings within the context of recent GWAS of AUD and other addiction phenotypes.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

12-2-2020

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