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 assoc...研究背景：近期相关综述指出，基于血液的甲基化生物标志物（blood-based methylation biomarkers）有望成为当前及未来酒精使用与成瘾的诊断及预后工具。由于血液与大脑等不同组织的甲基化模式往往存在大量重叠，基于血液的甲基化检测或许能够反映大脑内的甲基化变化；但目前针对这两类组织中酒精相关甲基化重叠情况的研究仍较为匮乏。 研究方法：为探究酒精对大脑甲基化组（methylome）的影响，并筛选可反映血液中此类变化的潜在生物标志物，我们对40只雄性DBA/2J小鼠的大脑与血液样本开展了全甲基化组关联研究（methylome-wide association study）。这些小鼠分别接受了急性乙醇（ethanol, EtOH）或生理盐水腹腔注射。为覆盖小鼠基因组中全部2200万个CpG位点（CpGs），我们采用甲基-CpG结合域（methyl-CpG binding domain, MBD）蛋白捕获技术富集甲基化基因组片段，随后进行下一代测序（next-generation sequencing，MBD-seq）。本研究开展了关联分析……