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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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)
Liu, C.; Marioni, R. E.; Hedman, Å. K.; Pfeiffer, L.; Tsai, P. -C.; Reynolds, L. M.; Just, A. C.; Duan, Q.; Boer, C. G.; Tanaka, T.; Elks, C. E.; Aslibekyan, S.; Brody, J. A.; Kühnel, B.; Herder, C.; Almli, L. M.; Zhi, D.; Wang, Y.; Huan, T.; Yao, C.; Mendelson, M. M.; Joehanes, R.; Liang, L.; Love, S. -A.; Guan, W.; Shah, S.; McRae, A. F.; Kretschmer, A.; Prokisch, H.; Strauch, K.; and Arnett, Donna K., "A DNA Methylation Biomarker of Alcohol Consumption" (2016). Epidemiology Faculty Publications. 35.