A DNA methylation biomarker of alcohol consumption.
| العنوان: | A DNA methylation biomarker of alcohol consumption. |
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| المؤلفون: | Liu, C, Marioni, R E, Hedman, Åsa K, Pfeiffer, L, Tsai, P-C, Reynolds, L M, Just, A C, Duan, Q, Boer, C G, Tanaka, T, Elks, C E, Aslibekyan, S, Brody, J A, Kühnel, B, Herder, C, Almli, L M, Zhi, D, Wang, Y, Huan, T, Yao, C, Mendelson, M M, Joehanes, R, Liang, L, Love, S-A, Guan, W, Shah, S, McRae, A F, Kretschmer, A, Prokisch, H, Strauch, K, Peters, A, Visscher, P M, Wray, N R, Guo, X, Wiggins, K L, Smith, A K, Binder, E B, Ressler, K J, Irvin, M R, Absher, D M, Hernandez, D, Ferrucci, L, Bandinelli, S, Lohman, K, Ding, J, Trevisi, L, Gustafsson, Stefan, Sandling, Johanna K., Stolk, L, Uitterlinden, A G, Yet, I, Castillo-Fernandez, J E, Spector, T D, Schwartz, J D, Vokonas, P, Lind, Lars, Li, Y, Fornage, M, Arnett, D K, Wareham, N J, Sotoodehnia, N, Ong, K K, van Meurs, J B J, Conneely, K N, Baccarelli, A A, Deary, I J, Bell, J T, North, K E, Liu, Y, Waldenberger, M, London, S J, Ingelsson, Erik, 1975, Levy, D |
| المصدر: | Molecular Psychiatry. 23:422-433 |
| الوصف: | 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. |
| وصف الملف: | electronic |
| الوصول الحر: | https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-319698Test https://doi.org/10.1038/mp.2016.192Test https://uu.diva-portal.org/smash/get/diva2:1087389/FULLTEXT01.pdfTest |
| قاعدة البيانات: | SwePub |
| تدمد: | 13594184 14765578 |
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| DOI: | 10.1038/mp.2016.192 |