Year: 2016
Type: article
Study design: Observational Study
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.
Source: Molecular Psychiatry
DOI: 10.1038/mp.2016.192
Authors: 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, 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, I J Deary, J T Bell, K E North, Y Liu, M Waldenberger, S J London, E Ingelsson, D Levy
Institutions: Boston University, National Heart, Lung, and Blood Institute, Framingham Heart Study, National Heart, Lung, and Blood Institute Division of Intramural Research, The University of Queensland, Institute of Genetics and Cancer, University of Edinburgh, Uppsala University, Science for Life Laboratory, Helmholtz Munich, King's College London, Wake Forest University Health Sciences, Wake Forest University, Icahn School of Medicine at Mount Sinai, University of North Carolina at Chapel Hill, Erasmus MC, National Institute on Aging, University of Cambridge, Wellcome/MRC Institute of Metabolic Science, MRC Epidemiology Unit, University of Alabama at Birmingham, University of Washington, Deutsches Diabetes-Zentrum e.V., German Center for Diabetes Research, Heinrich Heine University Düsseldorf, Emory University, The University of Texas Health Science Center at Houston, Harvard University, Hebrew SeniorLife, University of Minnesota, Institute for Molecular Bioscience, Institut für Humangenetik, Technical University of Munich, Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Ludwig-Maximilians-Universität München, German Centre for Cardiovascular Research, University of California, Los Angeles, Harbor–UCLA Medical Center, Max Planck Institute of Psychiatry, McLean Hospital, HudsonAlpha Institute for Biotechnology, National Institutes of Health, Azienda Sanitaria di Firenze, VA Boston Healthcare System, University of Kentucky, Columbia University, National Institute of Environmental Health Sciences, Stanford Medicine, Stanford University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,161
Funders: Wellcome Trust, Cancer Research UK, National Institute for Health and Care Research, National Institutes of Health, Medical Research Council, Biotechnology and Biological Sciences Research Council, Economic and Social Research Council, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Environmental Health Sciences, National Center for Advancing Translational Sciences
Awards: G1023702118, G1052397333, G1243299691, G125972088, G1261793039, MESA, CORONARY HEART DISEASE AND STROKE, G1276754516, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G1332411685, G1337262289, G1515649121, G1527150935, CORONARY HEART DISEASE AND STROKE, G1640378483, G1691174148, G173303992, G206690875, G2144938473, Rare variants and NHLBI traits in deeply phenotyped cohorts, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G22458031, G232264632, Genomics of Cardiac Electrical Activity and Arrhythmia, MESA, G247538147, G250621538, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, G270907595, G2800149121, MESA, G2837638605, G290884426, G291913881, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--EBCT READING, Design and Analysis of Sequencing-based Studies for Complex Human Traits, G2953103934, WGA Study to Identify Genetic Variants Associated with CV Events in CHS, G3114902838, Prospective meta-analyses of drug-gene interactions: CHARGE GWAS consortium, G3220743633, UCLA Clinical and Translational Science Institute, G34347772, G343705321, G3462919067, MESA, Epigenome-Wide Association Study of DNA Methylation and Atherosclerosis, G3939341824, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, Genomics of Sudden Cardiac Arrest Among African Americans, G423252844, TITLE: MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA), G4429312988, G4705346009, G4848485989, OPTION 3. 4/1/2014 - 3/31/2015. MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA) - READING CENTER, NHLBI, Epigenetic responses to social and environmental cues in early life and over the life course: impact on healthy ageing in UK population-based cohorts, MESA, G5067462658, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-ULTRASOUND, G5479317095, G5517677352, G5582818531, G567847597, G5897142711, CHS Events Follow-up Study, DNA Methylation as a Biomarker of Exposure and Effect for Particles and Metals, NIHR Senior Investigator Award, G6389927819, Institute for Clinical and Translational Research, The Framingham Heart Study, MESA, G6594529311, G661928818, G66341962, CHS-Transition Phase, G6957823285, G716312657, MESA, G740377980, NIHR Senior Investigator Award, G78770644, Clinical and Translational Science Award, G8864597167, G89064686, UCLA Clinical and Translational Science Institute, G905887895, G991334795
OpenAlex ID: W2552955852