A DNA methylation biomarker of alcohol consumption

Liu, C.; Marioni, R.; Hedman, A.; Pfeiffer, L.; Tsai, P-C; Reynolds, L.; Just, A.; Duan, Q.; Boer, C.; Tanaka, T.; Elks, C.; Aslibekyan, S.; Brody, J.; Kuehnel, B.; Herder, C.; Almli, L.; Zhi, D.; Wang, Y.; Huan, T.; Yao, C.; Mendelson, M.; Joehanes, R.; Liang, L.; Love, S-A; Guan, W.; Shah, S.; Mcrae, A.; Kretschmer, A.; Prokisch, H.; Strauch, K.; Peters, A.; Visscher, P.; Wray, N.; Guo, X.; Wiggins, K.; Smith, A.; Binder, E.; Ressler, K.; Irvin, M.; Absher, D.; Hernandez, D.; Ferrucci, L.; Bandinelli, S.; Lohman, K.; Ding, J.; Trevisi, L.; Gustafsson, S.; Sandling, J.; Stolk, L.; Uitterlinden, A.; YET, İDİL; Castillo-Fernandez, J.; Spector, T.; Schwartz, J.; Vokonas, P.; Lind, L.; Li, Y.; Fornage, M.; Arnett, D.; Wareham, N.; Sotoodehnia, N.; Ong, K.; van Meurs, J.; Conneely, K.; Baccarelli, A.; Deary, I.; Bell, J.; North, K.; Liu, Y.; Waldenberger, M.; London, S.; Ingelsson, E.; Levy, D.

doi:10.1038/mp.2016.192

A DNA methylation biomarker of alcohol consumption

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Liu C., Marioni R. E., Hedman A. K., Pfeiffer L., Tsai P., Reynolds L. M., ...More

MOLECULAR PSYCHIATRY, no.2, pp.422-433, 2018 (SCI-Expanded)

Publication Type: Article / Article
Publication Date: 2018
Doi Number: 10.1038/mp.2016.192
Journal Name: MOLECULAR PSYCHIATRY
Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
Page Numbers: pp.422-433
Hacettepe University Affiliated: No

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.