DNA methylation signature on phosphatidylethanol, not on self-reported alcohol consumption, predicts hazardous alcohol consumption in two distinct populations.,Molecular Psychiatry

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DNA methylation signature on phosphatidylethanol, not on self-reported alcohol consumption, predicts hazardous alcohol consumption in two distinct populations.
Molecular Psychiatry ( IF 9.6 ) Pub Date : 2020-02-07 , DOI: 10.1038/s41380-020-0668-x
Xiaoyu Liang _{1,

2} , Amy C Justice _{2,

3} , Kaku So-Armah ₄ , John H Krystal _{1,

2} , Rajita Sinha _{1,

5,

6} , Ke Xu _{1,

2}

Affiliation

The process of diagnosing hazardous alcohol drinking (HAD) is based on self-reported data and is thereby vulnerable to bias. There has been an interest in developing epigenetic biomarkers for HAD that might complement clinical assessment. Because alcohol consumption has been previously linked to DNA methylation (DNAm), we aimed to select DNAm signatures in blood to predict HAD from two demographically and clinically distinct populations (Ntotal = 1,549). We first separately conducted an epigenome-wide association study (EWAS) for phosphatidylethanol (PEth), an objective measure of alcohol consumption, and for self-reported alcohol consumption in Cohort 1. We identified 83 PEth-associated CpGs, including 23 CpGs previously associated with alcohol consumption or alcohol use disorder. In contrast, no CpG reached epigenome-wide significance on self-reported alcohol consumption. Using a machine learning approach, two CpG subsets from EWAS on PEth and on self-reported alcohol consumption from Cohort 1 were separately tested for the prediction of HAD in Cohort 2. We found that a subset of 143 CpGs selected from the EWAS on PEth showed an excellent prediction of HAD with the area under the receiver operating characteristic curve (AUC) of 89.4% in training set and 73.9% in validation set of Cohort 2. However, CpGs preselected from the EWAS on self-reported alcohol consumption showed a poor prediction of HAD with AUC 75.2% in training set and 57.6% in validation set. Our results demonstrate that an objective measure for alcohol consumption is a more informative phenotype than self-reported data for revealing epigenetic mechanisms. The PEth-associated DNAm signature in blood could serve as a robust biomarker for alcohol consumption.

中文翻译：

磷脂酰乙醇上的 DNA 甲基化特征（而不是自我报告的饮酒量）可以预测两个不同人群的危险饮酒量。

诊断危险饮酒 (HAD) 的过程基于自我报告的数据，因此很容易受到偏见的影响。人们一直对开发 HAD 表观遗传生物标志物感兴趣，以补充临床评估。由于先前已将饮酒与 DNA 甲基化 (DNAm) 联系起来，因此我们旨在选择血液中的 DNAm 特征来预测两个人口统计学和临床上不同的人群 (Ntotal = 1,549) 的 HAD。我们首先分别对磷脂酰乙醇 (PEth)（一种酒精消耗量的客观指标）以及队列 1 中自我报告的酒精消耗量进行了一项全表观基因组关联研究 (EWAS)。我们确定了 83 个与 PEth 相关的 CpG，其中包括 23 个之前关联的 CpG患有饮酒或酒精使用障碍。相比之下，没有 CpG 在自我报告的饮酒量方面达到表观基因组范围的显着性。使用机器学习方法，分别测试来自 PEth 上的 EWAS 和队列 1 中自我报告的饮酒量的两个 CpG 子集，以预测队列 2 中的 HAD。我们发现，从 PEth 上的 EWAS 中选择的 143 个 CpG 子集显示对 HAD 的预测非常出色，训练集中的受试者工作特征曲线下面积 (AUC) 为 89.4%，队列 2 的验证集中为 73.9%。然而，从 EWAS 中预选的关于自我报告的酒精消耗量的 CpG 表现出较差的预测HAD 的 AUC 在训练集中为 75.2%，在验证集中为 57.6%。我们的结果表明，与自我报告的数据相比，饮酒量的客观测量是一种更能提供信息的表型，可以揭示表观遗传机制。血液中与 PEth 相关的 DNAm 特征可以作为饮酒的强大生物标志物。

更新日期：2020-02-07

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