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A DNA methylation biomarker of alcohol consumption

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  • C. Liu
  • K. K. Hedman
  • L. Pfeiffer
  • P. C. Tsai
  • L. M. Reynolds
  • A. C. Just
  • Q. Duan
  • C. G. Boer
  • T. Tanaka
  • C. E. Elks
  • S. Aslibekyan
  • J. A. Brody
  • B. Kühnel
  • C. Herder
  • L. M. Almli
  • D. Zhi
  • Y. Wang
  • T. Huan
  • C. Yao
  • M. M. Mendelson
  • R. Joehanes
  • L. Liang
  • S. A. Love
  • W. Guan
  • S. Shah
  • A. F. McRae
  • A. Kretschmer
  • H. Prokisch
  • K. Strauch
  • A. Peters
  • P. M. Visscher
  • N. R. Wray
  • X. Guo
  • K. L. Wiggins
  • A. K. Smith
  • E. B. Binder
  • K. J. Ressler
  • M. R. Irvin
  • D. M. Absher
  • D. Hernandez
  • L. Ferrucci
  • S. Bandinelli
  • K. Lohman
  • J. Ding
  • L. Trevisi
  • S. Gustafsson
  • J. H. Sandling
  • L. Stolk
  • A. G. Uitterlinden
  • I. Yet
  • J. E. Castillo-Fernandez
  • T. D. Spector
  • J. D. Schwartz
  • P. Vokonas
  • L. Lind
  • Y. Li
  • M. Fornage
  • D. K. Arnett
  • N. J. Wareham
  • N. Sotoodehnia
  • K. K. Ong
  • J. B J van Meurs
  • K. N. Conneely
  • A. A. Baccarelli
  • J. T. Bell
  • K. E. North
  • Y. Liu
  • M. Waldenberger
  • S. J. London
  • E. Ingelsson
  • D. Levy

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Original languageEnglish
JournalMolecular Psychiatry
Early online date15 Nov 2016
DOIs
Publication statusE-pub ahead of print - 15 Nov 2016

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 (ntotal=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-7. Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P-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.Molecular Psychiatry advance online publication, 15 November 2016; doi:10.1038/mp.2016.192.

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