Investigation of DNA methylation changes in brain and blood associated with excessive alcohol consumption behavior in Wistar rats

Date

2023-8

Author

Günay, Berkay

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Alcohol use disorder (AUD) is a psychiatric disorder related with the inability to control alcohol use despite its devastating health, social, and economic consequences, and AUD-associated mortality rate is higher than that of many diseases with high mortality rates, including diabetes, tuberculosis, and HIV/AIDS. Despite such a high mortality rate, successful treatments are limited since the complex etiology of AUD is still not fully understood. Monozygotic twin studies have shown that AUD to be about 50-60% heritable and other studies on twins have found that epigenetic mechanisms play a role in the etiology of various psychiatric disorders. When studies examined the association of AUD and DNA methylation, one of the epigenetic mechanisms, they have shown that this is also the case for AUD. In this study, we investigated excessive alcohol consumption related DNA methylation alterations in four reward-related brain regions and blood in male and female wistar rats. Raw data obtained using reduced representation bisulfite sequencing (RRBS) technique were preprocessed, mapped to reference genome and differential methylation analysis was performed. We identified numerous differentially methylated cytosines (DMCs), regions (DMRs), and genes (DMGs) in each brain region and blood. Subsequent downstream analyses revealed that excessive alcohol consumption related DNA methylation alterations in wistar rats are sex-specific and mainly brain region-specific and tissue-specific. We also found that DNA methylation changes in Zfhx3, Foxn4, Gpr1, Gnas and Cmklr1 genes might be potential epigenetic biomarkers of AUD.

Subject Keywords

Alcohol use disorder, Alcohol deprivation effect, Reduced representation bisulfite sequencing, Wistar rats, Differential methylation

URI

https://hdl.handle.net/11511/105212

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Graduate School of Informatics, Thesis