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