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Article

A DNA methylation biomarker of alcohol consumption

by C Liu; RE Marioni; AK Hedman; L Pfeiffer; P-C Tsai; LM Reynolds; AC Just; Q Duan; CG Boer; T Tanaka; CE Elks; S Aslibekyan; JA Brody; B Kuehnel; C Herder; Lynn Almli; D Zhi; Y Wang; T Huan; C Yao; MM Mendelson; R Joehanes; L Liang; S-A Love; W Guan; S Shah; AF Mcrae; A Kretschmer; H Prokisch; K Strauch; A Peters; PM Visscher; NR Wray; X Guo; KL Wiggins; Alicia K Smith; EB Binder; Kerry Ressler; MR Irvin; DM Absher; D Hernandez; L Ferrucci; S Bandinelli; K Lohman; J Ding; L Trevisi; S Gustafsson; JH Sandling; L Stolk; AG Uitterlinden; I Yet; JE Castillo-Fernandez; TD Spector; JD Schwartz; P Vokonas; L Lind; Y Li; M Fornage; DK Arnett; NJ Wareham; N Sotoodehnia; KK Ong; JBJ van Meurs; Karen N Conneely; AA Baccarelli; IJ Deary; JT Bell; KE North; Y Liu; M Waldenberger; SJ London; E Ingelsson; D Levy

2018

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, Public Health
  • Biology, Genetics
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Abstract:Close

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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