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饮酒与全基因组 DNA 甲基化和表观遗传年龄加速的关联:个体水平和同卵双胞胎比较分析。

Associations of Alcohol Consumption With Epigenome-Wide DNA Methylation and Epigenetic Age Acceleration: Individual-Level and Co-twin Comparison Analyses.

机构信息

From the, Department of Psychology, (MS, JES, PB, DD), Virginia Commonwealth University, Richmond, Virginia.

Institute for Molecular Medicine Finland (FIMM), (SB, EC, JK, MO), University of Helsinki, Helsinki, Finland.

出版信息

Alcohol Clin Exp Res. 2021 Feb;45(2):318-328. doi: 10.1111/acer.14528. Epub 2020 Dec 30.

Abstract

BACKGROUND

DNA methylation may play a role in the progression from normative to problematic drinking and underlie adverse health outcomes associated with alcohol misuse. We examined the association between alcohol consumption and DNA methylation patterns using 3 approaches: a conventional epigenome-wide association study (EWAS); a co-twin comparison design, which controls for genetic and environmental influences that twins share; and a regression of age acceleration, defined as a discrepancy between chronological age and DNA methylation age, on alcohol consumption.

METHODS

Participants came from the Finnish Twin Cohorts (FinnTwin12/FinnTwin16; N = 1,004; 55% female; average age = 23 years). Individuals reported the number of alcoholic beverages consumed in the past week, and epigenome-wide DNA methylation was assessed in whole blood using the Infinium HumanMethylation450 BeadChip.

RESULTS

In the EWAS, alcohol consumption was significantly related to methylation at 24 CpG sites. When evaluating whether differences between twin siblings (185 monozygotic pairs) in alcohol consumption predicted differences in DNA methylation, co-twin comparisons replicated 4 CpG sites from the EWAS and identified 23 additional sites. However, when we examined qualitative differences in drinking patterns between twins (heavy drinker vs. light drinker/abstainer or moderate drinker vs. abstainer; 44 pairs), methylation patterns did not significantly differ within twin pairs. Finally, individuals who reported higher alcohol consumption also exhibited greater age acceleration, though results were no longer significant after controlling for genetic and environmental influences shared by co-twins.

CONCLUSIONS

Our analyses offer insight into the associations between epigenetic variation and levels of alcohol consumption in young adulthood.

摘要

背景

DNA 甲基化可能在从正常饮酒到问题饮酒的发展过程中起作用,并构成与酒精滥用相关的不良健康后果的基础。我们使用 3 种方法研究了饮酒与 DNA 甲基化模式之间的关系:常规全基因组关联研究(EWAS);双胞胎比较设计,该设计控制了双胞胎共享的遗传和环境影响;以及年龄加速的回归,定义为实际年龄与 DNA 甲基化年龄之间的差异与酒精消耗。

方法

参与者来自芬兰双胞胎队列(FinnTwin12/FinnTwin16;N=1004;55%为女性;平均年龄为 23 岁)。个体报告了过去一周内饮用的酒精饮料数量,并使用 Infinium HumanMethylation450 BeadChip 在全血中评估了全基因组 DNA 甲基化。

结果

在 EWAS 中,饮酒与 24 个 CpG 位点的甲基化显着相关。在评估双胞胎兄弟姐妹(185 对同卵双胞胎)之间的饮酒差异是否预测 DNA 甲基化的差异时,同卵双胞胎比较复制了 EWAS 中的 4 个 CpG 位点,并确定了另外 23 个位点。但是,当我们检查双胞胎之间饮酒模式的定性差异(重度饮酒者与轻度饮酒者/戒酒者或中度饮酒者与戒酒者;44 对)时,同卵双胞胎内的甲基化模式没有显着差异。最后,报告饮酒量较高的个体也表现出更大的年龄加速,尽管在控制了同卵双胞胎共享的遗传和环境影响后,结果不再显着。

结论

我们的分析为年轻人中表观遗传变异与饮酒水平之间的关联提供了深入的了解。

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