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A DNA methylation biomarker of alcohol consumption.
Wednesday,2017-05-10 15:27 America/Los_Angeles — ecterry
| Title | A DNA methylation biomarker of alcohol consumption. |
| Publication Type | Journal Article |
| Year of Publication | 2016 |
| Authors | 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 |
| Journal | Mol Psychiatry |
| Date Published | 2016 Nov 15 |
| ISSN | 1476-5578 |
| Abstract | <p>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.Molecular Psychiatry advance online publication, 15 November 2016; doi:10.1038/mp.2016.192.</p> |
| DOI | 10.1038/mp.2016.192 |
| Alternate Journal | Mol. Psychiatry |
| PubMed ID | 27843151 |
| Grant List | MC_UU_12015/1 / / Medical Research Council / United Kingdom MR/K026992/1 / / Medical Research Council / United Kingdom R01 HL101250 / HL / NHLBI NIH HHS / United States |
ePub date:
16/11