Epigenome-Wide DNA Methylation Association Analysis Identified Novel Loci in Peripheral Cells for Alcohol Consumption Among European American Male Veterans.
Epigenome-Wide DNA Methylation Association Analysis Identified Novel Loci in Peripheral Cells for Alcohol Consumption Among European American Male Veterans.
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全基因组DNA甲基化关联分析鉴定了外围细胞中的新基因座，以供欧美男性退伍军人饮酒。
DOI：
10.1111/acer.14168
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发表时间：
2019-10
期刊：
影响因子：
--
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文献类型：
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有害饮酒会产生严重的不良医疗后果。这些效应可能部分是通过DNA甲基化的改变来调节的。因此，外周细胞中的DNA甲基化特征可能为酒精使用的医疗影响和未来酒精消费的风险提供生物标记物。使用高密度甲基化阵列，我们研究了一大群欧洲裔美国退伍军人中与饮酒有关的唾液细胞表观基因组DNA甲基化。在这项研究中，对1135名欧洲裔美国男性的超过87万个CpG DNA位点的DNA甲基化进行了分析。使用酒精使用障碍识别测试-饮酒(AUDIT-C)评估饮酒情况。将线性回归应用于表观基因组范围的关联研究，并对混杂因素进行了调整。在KEGG数据库中进行基因集浓缩分析，并对基因长度进行校正。我们发现共有70个CpG位点达到了EWAS校正后的显著水平(p<；6E-08)，单个CpG位点对饮酒的影响很小，包括新的CpG位点和6个先前报道的与酒精使用障碍、肝功能、体重指数和脂肪代谢相关的CpG位点。最显著的CpG位点位于SLC7A11(t=−11.34，p=2.66E-28)，这是一个与半胱氨酸和谷氨酸运输有关的基因。70个重要的CpG位点位于44个基因上，其中包括与氨基酸运输和代谢系统相关的基因。我们识别了68条路径，错误发现率为0.05。我们发现了与饮酒有关的新的DNA甲基化位点。研究结果可能有助于揭示大量饮酒者饮酒对不良健康后果的外围机制。
Hazardous alcohol consumption has significant adverse medical consequences. These effects may be mediated, in part, by alterations in DNA methylation. Thus, DNA methylation signatures in peripheral cells may provide biomarkers of the medical impact of alcohol use and the risk for future alcohol consumption. Using a high density methylation array, we characterized epigenome-wide DNA methylation in saliva cells with respect to alcohol consumption in a large cohort of male European American veterans. In this study, DNA methylation of over 870,000 CpG DNA sites was profiled in 1,135 European American men. Alcohol consumption was assessed using the Alcohol Use Disorder Identification Test-Consumption (AUDIT-C). Linear regression was applied in an epigenome-wide association study (EWAS), adjusted for confounders. Gene set enrichment analysis was performed in the KEGG database with a correction for gene length. We found that a total of 70 CpG sites reached EWAS-corrected significance (p<6E-08) with small effects on alcohol consumption for individual CpG sites, including 64 new CpG sites and six CpG sites that were previously reported as associated with alcohol use disorder, liver function, body mass index, and lipid metabolism. The most significant CpG site was located in SLC7A11(t=−11.34, p=2.66E-28), a gene involved specifically in cysteine and glutamate transportation. The 70 significant CpG sites were located on 44 genes, including genes involved in amino acid transport and metabolism systems. We identified 68 pathways with a false discovery rate <0.05. We identified novel DNA methylation sites associated with alcohol consumption. Results may shed light on peripheral mechanisms of alcohol consumption on adverse health outcomes among heavy drinkers.
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DOI：
10.1176/appi.ajp.2018.17060595
发表时间：
2018-08-01
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Han LKM;Aghajani M;Clark SL;Chan RF;Hattab MW;Shabalin AA;Zhao M;Kumar G;Xie LY;Jansen R;Milaneschi Y;Dean B;Aberg KA;van den Oord EJCG;Penninx BWJH
通讯作者：
Penninx BWJH
影响因子：
16.2
作者：
Freiberg, MS;Cabral, HJ;Ellison, RC
通讯作者：
Ellison, RC
影响因子：
4.6
作者：
Brueckmann, Christof;Islam, Sumaiya A.;Nieratschker, Vanessa
通讯作者：
Nieratschker, Vanessa
影响因子：
3.4
作者：
Heberlein, Annemarie;Muschler, Marc;Hillemacher, Thomas
通讯作者：
Hillemacher, Thomas
影响因子：
4.4
作者：
Hearn, Nerissa L.;Coleman, Aaron S.;Lind, Joanne M.
通讯作者：
Lind, Joanne M.