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Author Notes:

The Population Sciences Branch, Division of Intramural Research, The Framingham Heart Study, National Heart, Lung and Blood Institute, Perini Building, Framingham, MA 01701, USA. E-mail: chunyu.liu@nih.gov or levyd@nhlbi.nih.gov

C Liu, R E Marioni, Å K Hedman, L Pfeiffer, P-C Tsai, L M Reynolds, A C Just, Q Duan, C G Boer & T Tanaka: These authors contributed equally to this work.

K E North, Y Liu, M Waldenberger, S J London, E Ingelsson & D Levy: These authors jointly supervised the work.

The meta-analysis results for the continuous and categorical alcohol consumption traits can be downloaded from the database of Genotypes and Phenotypes (dbGaP) CHARGE Summary site under accession phs000930.

DNA methylation measurements by several cohorts have been deposited in dbGap.

Contact information for obtaining DNA methylation measurements from the European cohorts and some of the American cohorts is available upon request.

Detailed acknowledgments were included in Supplementary Information.

Erik Ingelsson is an advisor and consultant for Precision Wellness Inc (Redwood City, CA).

The remaining authors declare no conflict of interest.

Subjects:

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Neurosciences
  • Psychiatry
  • Neurosciences & Neurology
  • GABA(B) RECEPTOR
  • DISEASE
  • DEPENDENCE
  • BURDEN
  • METAANALYSIS
  • ASSOCIATION
  • MICROARRAY
  • EXPRESSION
  • METHYLOME
  • BODY

A DNA methylation biomarker of alcohol consumption

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Journal Title:

Molecular Psychiatry

Volume:

Volume 23, Number 2

Publisher:

, Pages 422-433

Type of Work:

Article | Final Publisher PDF

Abstract:

The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (n total = 13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n = 6926) and identified 144 CpGs that provided substantial discrimination (area under the curve = 0.90-0.99) for current heavy alcohol intake (≥42 g per day in men and ≥28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P < 1×10 -7 . Analysis of the monocyte-derived DNA (n = 1251) identified 62 alcohol-related CpGs at P < 1×10 -7 . In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.

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© 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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