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A DNA methylation biomarker of alcohol consumption.

Publication ,  Journal Article
Liu, C; Marioni, RE; Hedman, ÅK; Pfeiffer, L; Tsai, P-C; Reynolds, LM; Just, AC; Duan, Q; Boer, CG; Tanaka, T; Elks, CE; Aslibekyan, S; Li, Y ...
Published in: Mol Psychiatry
February 2018

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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Published In

Mol Psychiatry

DOI

EISSN

1476-5578

Publication Date

February 2018

Volume

23

Issue

2

Start / End Page

422 / 433

Location

England

Related Subject Headings

  • White People
  • Psychiatry
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study
  • Female
  • Ethanol
  • Epigenesis, Genetic
  • DNA Methylation
 

Citation

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Liu, C., Marioni, R. E., Hedman, Å. K., Pfeiffer, L., Tsai, P.-C., Reynolds, L. M., … Levy, D. (2018). A DNA methylation biomarker of alcohol consumption. Mol Psychiatry, 23(2), 422–433. https://doi.org/10.1038/mp.2016.192
Liu, C., R. E. Marioni, Å. K. Hedman, L. Pfeiffer, P. -. C. Tsai, L. M. Reynolds, A. C. Just, et al. “A DNA methylation biomarker of alcohol consumption.Mol Psychiatry 23, no. 2 (February 2018): 422–33. https://doi.org/10.1038/mp.2016.192.
Liu C, Marioni RE, Hedman ÅK, Pfeiffer L, Tsai P-C, Reynolds LM, et al. A DNA methylation biomarker of alcohol consumption. Mol Psychiatry. 2018 Feb;23(2):422–33.
Liu, C., et al. “A DNA methylation biomarker of alcohol consumption.Mol Psychiatry, vol. 23, no. 2, Feb. 2018, pp. 422–33. Pubmed, doi:10.1038/mp.2016.192.
Liu C, Marioni RE, Hedman ÅK, Pfeiffer L, Tsai P-C, Reynolds LM, Just AC, Duan Q, Boer CG, Tanaka T, Elks CE, Aslibekyan S, Brody JA, Kühnel B, Herder C, Almli LM, Zhi D, Wang Y, Huan T, Yao C, Mendelson MM, Joehanes R, Liang L, Love S-A, Guan W, Shah S, McRae AF, Kretschmer A, Prokisch H, Strauch K, Peters A, Visscher PM, Wray NR, Guo X, Wiggins KL, Smith AK, Binder EB, Ressler KJ, Irvin MR, Absher DM, Hernandez D, Ferrucci L, Bandinelli S, Lohman K, Ding J, Trevisi L, Gustafsson S, Sandling JH, Stolk L, Uitterlinden AG, Yet I, Castillo-Fernandez JE, Spector TD, Schwartz JD, Vokonas P, Lind L, Li Y, Fornage M, Arnett DK, Wareham NJ, Sotoodehnia N, Ong KK, van Meurs JBJ, Conneely KN, Baccarelli AA, Deary IJ, Bell JT, North KE, Liu Y, Waldenberger M, London SJ, Ingelsson E, Levy D. A DNA methylation biomarker of alcohol consumption. Mol Psychiatry. 2018 Feb;23(2):422–433.

Published In

Mol Psychiatry

DOI

EISSN

1476-5578

Publication Date

February 2018

Volume

23

Issue

2

Start / End Page

422 / 433

Location

England

Related Subject Headings

  • White People
  • Psychiatry
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study
  • Female
  • Ethanol
  • Epigenesis, Genetic
  • DNA Methylation