A DNA methylation biomarker of alcohol consumption

C. Liu, R. E. Marioni, K. 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. YaoM. 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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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-7. Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P-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.Molecular Psychiatry advance online publication, 15 November 2016; doi:10.1038/mp.2016.192.

Original languageEnglish
JournalMolecular Psychiatry
Early online date15 Nov 2016
Publication statusE-pub ahead of print - 15 Nov 2016


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