A DNA methylation biomarker of alcohol consumption

• Type of Material: Article
• Authors: C Liu, The Framingham Heart Study; RE Marioni, National Heart, Lung and Blood Institute; AK Hedman, Boston University; L Pfeiffer, University of Edinburgh; P-C Tsai, University of Edinburgh; LM Reynolds, University of Queensland; AC Just, Uppsala University; Q Duan, Helmholtz Zentrum Munchen; CG Boer, Helmholtz Zentrum Munchen; T Tanaka, Kings College London; CE Elks, Wake Forest School of Medicine; S Aslibekyan, Icahn School of Medicine at Mount Sinai; JA Brody, University of North Carolina; B Kuehnel, Erasmus MC; C Herder, National Institute on Aging; Lynn Almli, Emory University; D Zhi, University of Alabama Birmingham; Y Wang, University of Washington; T Huan, German Center for Diabetes Research (DZD); C Yao, Heinrich Heine University Düsseldorf; MM Mendelson, Emory University; R Joehanes, University of Texas Health Science Center at Houston; L Liang, University of North Carolina; S-A Love, Harvard Medical School; W Guan, Harvard University; S Shah, University of Minnesota; AF Mcrae, University of Queensland; A Kretschmer, Helmholtz Zentrum Munchen; H Prokisch, Technical University of Munich; K Strauch, Ludwig-Maximilians-Universität München; A Peters, Helmholtz Zentrum Munchen; PM Visscher, DZHK (German Centre for Cardiovascular Research); NR Wray, University of California Los Angeles; X Guo, Max-Planck Institute of Psychiatry; KL Wiggins, McLean Hospital; Alicia K Smith, Emory University; EB Binder, National Institutes of Health; Kerry Ressler, Emory University; MR Irvin, Wake Forest School of Medicine; DM Absher, Harvard T.H. Chan School of Public Health; D Hernandez, Uppsala University; L Ferrucci, Uppsala University; S Bandinelli, Azienda Sanitaria Firenze (ASF); K Lohman, Harvard T.H. Chan School of Public Health; J Ding, VA Boston Healthcare System; L Trevisi, Uppsala University; S Gustafsson, University of North Carolina; JH Sandling, University of Texas Health Science Center at Houston; L Stolk, University of Kentucky; AG Uitterlinden, Emory University; I Yet, Columbia University; JE Castillo-Fernandez, University of Edinburgh; TD Spector, National Institute of Environmental Health Sciences; JD Schwartz, Stanford University; P Vokonas, VA Boston Healthcare System; L Lind, Uppsala University; Y Li, University of North Carolina; M Fornage, University of Texas Health Science Center at Houston; DK Arnett, University of Kentucky; NJ Wareham, University of Cambridge; N Sotoodehnia, University of Washington; KK Ong, University of Cambridge; JBJ van Meurs, Erasmus MC; Karen N Conneely, Emory University; AA Baccarelli, Columbia University; IJ Deary, University of Edinburgh; JT Bell, King’s College London; KE North, University of North Carolina at Chapel Hill; Y Liu, Wake Forest School of Medicine; M Waldenberger, Helmholtz Zentrum München; SJ London, National Institute of Environmental Health Sciences; E Ingelsson, Uppsala University; D Levy, National Heart, Lung and Blood Institute
• Language: English
• Date: 2018-02-01
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/mp.2016.192
• Title of Journal or Parent Work: Molecular Psychiatry
• ISSN: 1359-4184
• Volume: 23
• Issue: 2
• Start Page: 422
• End Page: 433
• Keywords: Biochemistry & Molecular Biology; DEPENDENCE; Neurosciences & Neurology; Psychiatry; Science & Technology; BURDEN; METAANALYSIS; Life Sciences & Biomedicine; GABA(B) RECEPTOR; ASSOCIATION; MICROARRAY; EXPRESSION; BODY; METHYLOME; DISEASE; Neurosciences
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Public Health; Biology, Genetics

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.