Abstract
BackgroundRecently, 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.ResultsIn 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.ConclusionsThe 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.
Highlights
An alcohol predictor was developed using Deoxyribonucleic acid (DNA) methylation at 144 CpG sites (DNAm-Alc) as a biomarker for improved clinical or epidemiologic assessment of alcohol-related ill health
We considered whether the suggestive relationship between DNAm-Alc levels at birth and Alcohol Use Disorders Identification Test (AUDIT) in adolescence could have been driven by maternal drinking during in utero development, but this did not appear to be the case in follow-up analysis that added examination of maternal DNAm-Alc during pregnancy and which failed to show effects independent of DNAm-Alc at birth (Additional file 7)
We demonstrated the DNAm-Alc score shows a stronger correlation for sustained alcohol use compared to shorter-term alcohol use, as evidenced by the higher proportion of the variance explained at midlife than in adolescence, and for AUDIT score compared to cross-sectional weekly alcohol intake
Summary
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. Alcohol use and misuse are responsible for a large proportion of the global burden of disease [1]; measuring alcohol exposure in epidemiological studies presents a number of challenges. Self-reported alcohol intake is the most commonly used source of information, but such measurements are fraught with both error and bias, and generally underestimate exposure [2, 3]. The latter is often more pronounced at higher levels of exposure as heavy drinkers can lose track of their intake or differentially under-report their consumption compared to light drinkers, which may result in an overestimation of the effects of alcohol and an underestimation of the burden of disease. Similar bias can occur in retrospective studies where the quality of self-reported alcohol use can vary between cases and controls
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