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Liu, C.; Marioni, R. E.; Hedman, A. K.; Pfeiffer, L.; Tsai, P-C; Reynolds, L. M.; Just, A. C.; Duan, Q.; Bör, C. G.; Tanaka, T.; Elks, C. E.; Aslibekyan, S.; Brody, J. A.; Kuehnel, 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.; Peters, A.; Visscher, P. M.; Wray, N. R.; Guo, X.; Wiggins, K. L.; Smith, A. K.; Binder, E. B.; Ressler, K. J.; Irvin, M. R.; Absher, D. M.; Hernandez, D.; Ferrucci, L.; Bandinelli, S.; Lohman, K.; Ding, J.; Trevisi, L.; Gustafsson, S.; Sandling, J. H.; Stolk, L.; Uitterlinden, A. G.; Yet, I.; Castillo-Fernandez, J. E.; Spector, T. D.; Schwartz, J. D.; Vokonas, P.; Lind, L.; Li, Y.; Fornage, M.; Arnett, D. K.; Wareham, N. J.; Sotoodehnia, N.; Ong, K. K.; vMeurs, J. B. J. van; Conneely, K. N.; Baccarelli, A. A.; Deary, I. J.; Bell, J. T.; North, K. E.; Liu, Y.; Waldenberger, M.; London, S. J.; Ingelsson, E.; Levy, D. (2018): A DNA methylation biomarker of alcohol consumption. In: Molecular Psychiatry, Vol. 23, No. 2: pp. 422-433
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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 x 10(-7). Analysis of the monocyte-derived DNA (n = 1251) identified 62 alcohol-related CpGs at P < 1 x 10(-7). In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the gamma-Aminobutyric acid-A receptor delta and gamma-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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