MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS82BN, UK.
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Clin Epigenetics. 2019 Nov 27;11(1):163. doi: 10.1186/s13148-019-0753-7.
Recently, an alcohol predictor was developed using DNA methylation at 144 CpG sites (DNAm-Alc) as a biomarker for improved clinical or epidemiologic assessment of alcohol-related ill health. We validate the performance and characterise the drivers of this DNAm-Alc for the first time in independent populations.
In N = 1049 parents from the Avon Longitudinal Study of Parents and Children (ALSPAC) Accessible Resource for Integrated Epigenomic Studies (ARIES) at midlife, we found DNAm-Alc explained 7.6% of the variation in alcohol intake, roughly half of what had been reported previously, and interestingly explained a larger 9.8% of Alcohol Use Disorders Identification Test (AUDIT) score, a scale of alcohol use disorder. Explanatory capacity in participants from the offspring generation of ARIES measured during adolescence was much lower. However, DNAm-Alc explained 14.3% of the variation in replication using the Head and Neck 5000 (HN5000) clinical cohort that had higher average alcohol consumption. To investigate whether this relationship was being driven by genetic and/or earlier environment confounding, we examined how earlier versus concurrent DNAm-Alc measures predicted AUDIT scores. In both ARIES parental and offspring generations, we observed associations between AUDIT and concurrent, but not earlier DNAm-Alc, suggesting independence from genetic and stable environmental contributions.
The stronger relationship between DNAm-Alcs and AUDIT in parents at midlife compared to adolescents despite similar levels of consumption suggests that DNAm-Alc likely reflects long-term patterns of alcohol abuse. Such biomarkers may have potential applications for biomonitoring and risk prediction, especially in cases where reporting bias is a concern.
最近，一种使用 144 个 CpG 位点的 DNA 甲基化（DNAm-Alc）作为生物标志物的酒精预测器被开发出来，用于改善对与酒精相关的不良健康的临床或流行病学评估。我们首次在独立人群中验证了这种 DNAm-Alc 的性能，并对其驱动因素进行了描述。
在 N = 1049 名来自阿冯纵向研究父母和儿童（ALSPAC）可访问资源综合表观基因组学研究（ARIES）的中年人父母中，我们发现 DNAm-Alc 解释了酒精摄入量变化的 7.6%，大约是之前报道的一半，有趣的是，它还解释了酒精使用障碍识别测试（AUDIT）评分的更大变化，AUDIT 是一个衡量酒精使用障碍的量表。在 ARIES 后代队列中，在青少年时期测量的参与者的解释能力要低得多。然而，DNAm-Alc 解释了使用头部和颈部 5000（HN5000）临床队列的复制的 14.3%的变化，该队列的平均酒精摄入量更高。为了研究这种关系是否受到遗传和/或早期环境混杂因素的影响，我们研究了早期与同期的 DNAm-Alc 测量值如何预测 AUDIT 评分。在 ARIES 父母和后代两代中，我们观察到 AUDIT 与同期的 DNAm-Alc 相关，而与早期的 DNAm-Alc 无关，这表明 DNAm-Alc 独立于遗传和稳定的环境因素。
尽管父母的酒精摄入量与青少年相似，但在中年父母中，DNAm-Alc 与 AUDIT 之间的关系更强，这表明 DNAm-Alc 可能反映了长期的酒精滥用模式。这种生物标志物可能具有生物监测和风险预测的应用潜力，特别是在报告偏差是一个问题的情况下。
