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Prefrontal cortex eQTLs/mQTLs enriched in genetic variants associated with alcohol use disorder and other diseases

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Summary: Environmental factors, such as substance abuse and stress, can lead to lasting changes in gene expression regulation in the brain through mechanisms like DNA methylation. This study found that chronic alcohol consumption results in significantly increased methylation of NR3C1 exon variant 1(H) and an increase in 5-hydroxymethylcytosine levels over 5-methylcytosine. These DNA methylation changes were associated with reduced NR3C1 mRNA and protein expression levels in the prefrontal cortex and other cortico-limbic regions of individuals with alcohol use disorder. Additionally, the expression of stress-related genes in the prefrontal cortex and hippocampus of these individuals was altered, suggesting a potential role of aberrant DNA methylation of NR3C1 and other stress-related genes in the pathophysiology of alcohol use disorder.

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