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Validation and characterization of a DNA methylation alcohol biomarker across the life course

Research output: Contribution to journalArticle

Original languageEnglish
Article number163 (2019)
Pages (from-to)163
Number of pages12
JournalClinical Epigenetics
Volume11
Issue number1
DOIs
DateSubmitted - 28 Mar 2019
DateAccepted/In press - 23 Sep 2019
DatePublished (current) - 27 Nov 2019

Abstract

Background:
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 characterize the drivers of this DNAm-Alc for the first time in independent populations.

Results:
In N=1,049 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 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 vs. 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.

Conclusions:
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.

    Research areas

  • ALSPAC, AUDIT, prediction, CHARGE, alcohol use disorder

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via BMC at https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-019-0753-7 . Please refer to any applicable terms of use of the publisher.

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    Licence: CC BY

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