Data from: 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

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.