A Whole Methylome Study of Ethanol Exposure in Brain and Blood: An Exploration of the Utility of Peripheral Blood as Proxy Tissue for Brain in Alcohol Methylation Studies. (11th November 2018)

• Record Type: Journal Article
• Authors: Clark, Shaunna L.; Costin, Blair N.; Chan, Robin F.; Johnson, Alexander W.; Xie, Linying; Jurmain, Jessica L.; Kumar, Gaurav; Shabalin, Andrey A.; Pandey, Ashutosh K.; Aberg, Karolina A.; Miles, Michael F.; van den Oord, Edwin
• Is Part Of: Alcoholism. Volume 42:Number 12(2018)
• Page Start: 2360
• Page End: 2368
• Publication Date: 2018-11-11
• Subjects: Alcohol -- Epigenetics -- Glutamate -- Biomarker -- Methylation; Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.13905
• Languages: English
• ISSNs: 0145-6008

Abstract

Abstract : Background: Recent reviews have highlighted the potential use of blood‐based methylation biomarkers as diagnostic and prognostic tools of current and future alcohol use and addiction. Due to the substantial overlap that often exists between methylation patterns across different tissues, including blood and brain, blood‐based methylation may track methylation changes in brain; however, little work has explored the overlap in alcohol‐related methylation in these tissues. Methods: To study the effects of alcohol on the brain methylome and identify possible biomarkers of these changes in blood, we performed a methylome‐wide association study in brain and blood from 40 male DBA/2J mice that received either an acute ethanol (EtOH) or saline intraperitoneal injection. To investigate all 22 million CpGs in the mouse genome, we enriched for the methylated genomic fraction using methyl‐CpG binding domain (MBD) protein capture followed by next‐generation sequencing (MBD‐seq). We performed association tests in blood and brain separately followed by enrichment testing to determine whether there was overlapping alcohol‐related methylation in the 2 tissues. Results: The top result for brain was a CpG located in an intron of Ttc39b ( p = 5.65 × 10 −08 ), and for blood, the top result was located in Espnl ( p = 5.11 × 10 −08 ). Analyses implicated pathways involved in inflammation and neuronal differentiation, such as CXCR4, IL‐7, and Wnt signaling. Enrichment tests indicated significant overlap among the top results in brain and blood. Pathway analyses of the overlapping genes converge on MAPKinase signaling ( p = 5.6 × 10 −05 ) which plays a central role in acute and chronic responses to alcohol and glutamate receptor pathways, which can regulate neuroplastic changes underlying addictive behavior. Conclusions: Overall, we have shown some methylation changes in brain and blood after acute EtOH administration and that the changes in blood partly mirror the changes in brain suggesting the potential for DNA methylation in blood to be biomarkers of alcohol use. Abstract : We identified methylation changes in both brain and blood after acute EtOH administration. Our results show overlapping methylation signals in blood and brain suggesting alcohol‐related methylation in blood partly, but not fully, mirrors changes occurring in brain tissue. These findings have important potential implications for the clinical application of blood biomarkers as it provides preliminary evidence that methylation in blood might be used as a proxy tissue to detect some process that occurs in brain as a result of EtOH.