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A DNA methylation biomarker of alcohol consumption.

Liu, C (author)
Marioni, R E (author)
Hedman, Åsa K (author)
Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab
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Pfeiffer, L (author)
Tsai, P-C (author)
Reynolds, L M (author)
Just, A C (author)
Duan, Q (author)
Boer, C G (author)
Tanaka, T (author)
Elks, C E (author)
Aslibekyan, S (author)
Brody, J A (author)
Kühnel, B (author)
Herder, C (author)
Almli, L M (author)
Zhi, D (author)
Wang, Y (author)
Huan, T (author)
Yao, C (author)
Mendelson, M M (author)
Joehanes, R (author)
Liang, L (author)
Love, S-A (author)
Guan, W (author)
Shah, S (author)
McRae, A F (author)
Kretschmer, A (author)
Prokisch, H (author)
Strauch, K (author)
Peters, A (author)
Visscher, P M (author)
Wray, N R (author)
Guo, X (author)
Wiggins, K L (author)
Smith, A K (author)
Binder, E B (author)
Ressler, K J (author)
Irvin, M R (author)
Absher, D M (author)
Hernandez, D (author)
Ferrucci, L (author)
Bandinelli, S (author)
Lohman, K (author)
Ding, J (author)
Trevisi, L (author)
Gustafsson, Stefan (author)
Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab
Sandling, Johanna K. (author)
Uppsala universitet,Molekylär medicin,Reumatologi,Science for Life Laboratory, SciLifeLab
Stolk, L (author)
Uitterlinden, A G (author)
Yet, I (author)
Castillo-Fernandez, J E (author)
Spector, T D (author)
Schwartz, J D (author)
Vokonas, P (author)
Lind, Lars (author)
Uppsala universitet,Kardiovaskulär epidemiologi
Li, Y (author)
Fornage, M (author)
Arnett, D K (author)
Wareham, N J (author)
Sotoodehnia, N (author)
Ong, K K (author)
van Meurs, J B J (author)
Conneely, K N (author)
Baccarelli, A A (author)
Deary, I J (author)
Bell, J T (author)
North, K E (author)
Liu, Y (author)
Waldenberger, M (author)
London, S J (author)
Ingelsson, Erik, 1975- (author)
Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA
Levy, D (author)
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 (creator_code:org_t)
2016-11-15
2018
English.
In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23, s. 422-433
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Other Basic Medicine (hsv//eng)

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