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.
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.
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DOI：
10.1111/acer.13905
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
van den Oord E
中科院分区：
文献类型：
--
作者：
Clark SL;Costin BN;Chan RF;Johnson AW;Xie L;Jurmain JL;Kumar G;Shabalin AA;Pandey AK;Aberg KA;Miles MF;van den Oord E
最近的综述强调了基于血液的甲基化生物标记物作为当前和未来酒精使用和成瘾的诊断和预后工具的潜在用途。由于不同组织(包括血液和脑)的甲基化模式之间经常存在大量重叠，基于血液的甲基化可能跟踪大脑中的甲基化变化，然而，很少有工作探索这些组织中与酒精相关的甲基化重叠。为了研究酒精对大脑甲基组的影响，并确定血液中这些变化的可能生物标志物，我们对40只接受急性乙醇或生理盐水腹腔注射的雄性DBA/2J小鼠的大脑和血液进行了一项甲基组关联研究。为了研究小鼠基因组中的全部2200万个CpG，我们使用甲基-CpG结合结构域(MBD)蛋白捕获和下一代测序(MBD-SEQ)来富集甲基化基因组部分。我们分别在血液和大脑中进行关联测试，然后进行浓缩测试，以确定这两个组织中是否存在重叠的酒精相关甲基化。脑的最高结果是位于Ttc39b内含子的CpG(p=5.65×10−08)，血液的最高结果位于ESPN1(p=5.11×10−08)。分析参与炎症和神经元分化的相关通路，如CXCR4、IL-7和Wnt信号。浓缩测试表明，在大脑和血液中的顶级结果之间存在显著重叠。这些重叠基因的通路分析集中在MAPKinase信号通路上(p=5.6x10−05)，MAPKinase信号通路在酒精和谷氨酸受体通路的急性和慢性反应中发挥核心作用，该通路可以调节成瘾行为潜在的神经可塑性变化。总体而言，我们已经显示了急性乙醇注射后大脑和血液中的一些甲基化变化，血液中的变化在一定程度上反映了大脑的变化，这表明血液中的DNA甲基化可能成为酒精使用的生物标志物。
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. 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 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 if there was overlapping alcohol related methylation in the two tissues. 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. Overall, we have shown some methylation changes in brain and blood after acute ethanol 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.
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DOI：
10.1111/acer.13362
发表时间：
2017-05
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Adkins AE;Hack LM;Bigdeli TB;Williamson VS;McMichael GO;Mamdani M;Edwards AC;Aliev F;Chan RF;Bhandari P;Raabe RC;Alaimo JT;Blackwell GG;Moscati A;Poland RS;Rood B;Patterson DG;Walsh D;Collaborative Study of the Genetics of Alcoholism Consortium;Whitfield JB;Zhu G;Montgomery GW;Henders AK;Martin NG;Heath AC;Madden PAF;Frank J;Ridinger M;Wodarz N;Soyka M;Zill P;Ising M;Nöthen MM;Kiefer F;Rietschel M;German Study of the Genetics of Addiction Consortium;Gelernter J;Sherva R;Koesterer R;Almasy L;Zhao H;Kranzler HR;Farrer LA;Maher BS;Prescott CA;Dick DM;Bacanu SA;Mathies LD;Davies AG;Vladimirov VI;Grotewiel M;Bowers MS;Bettinger JC;Webb BT;Miles MF;Kendler KS;Riley BP
通讯作者：
Riley BP
DOI：
10.1177/1073858415579635
发表时间：
2015-10
期刊：
The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
影响因子：
--
作者：
Heyward FD;Sweatt JD
通讯作者：
Sweatt JD
影响因子：
--
作者：
Koob, George F
通讯作者：
Koob, George F
影响因子：
7
作者：
Guénet, JL
通讯作者：
Guénet, JL
在大型多种族基因组的关联研究中，饮酒差异的遗传因素因种族/种族而异。
影响因子：
11
作者：
Jorgenson E;Thai KK;Hoffmann TJ;Sakoda LC;Kvale MN;Banda Y;Schaefer C;Risch N;Mertens J;Weisner C;Choquet H
通讯作者：
Choquet H