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Mol Psychiatry. 2018 Feb;23(2):422-433. doi: 10.1038/mp.2016.192. Epub 2016 Nov 15.

A DNA methylation biomarker of alcohol consumption.

Author information

1
The Framingham Heart Study, Framingham, MA, USA.
2
The Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, MD, USA.
3
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
4
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
5
Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
6
Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
7
Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
8
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
9
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
10
Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
11
Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
12
Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
13
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
14
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
15
Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
16
MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
17
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
18
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
19
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
20
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.
21
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
22
School of Biomedical Informatics and School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
23
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
24
Hebrew SeniorLife, Harvard Medical School, Boston, MA, USA.
25
Harvard School of Public Health, Harvard University, Boston, MA, USA.
26
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
27
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
28
Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
29
Institute of Human Genetics, Technische Universität München, München, Germany.
30
Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.
31
Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
32
DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
33
Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA.
34
Max-Planck Institute of Psychiatry, Munich, Germany.
35
Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA.
36
HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
37
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
38
Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy.
39
Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
40
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
41
Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
42
Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
43
Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
44
Departments of Environmental Health and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
45
VA Boston Healthcare System and Boston University Schools of Public Health and Medicine, Jamaica Plain, MA, USA.
46
Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
47
Department of Genetics, Department of Biostatistics and Department of Computer Science, University of North Carolina, Chapel Hill, NC, USA.
48
Institute of Molecular Medicine and Human Genetics Center, University of Texas Health Science Center at Houston, Houston TX, USA.
49
College of Public Health, University of Kentucky, Lexington, KY, USA.
50
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
51
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
52
Department of Psychology, University of Edinburgh, Edinburgh, UK.
53
Department of Health and Human Services, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
54
Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.

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<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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