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Liu, C.* ; Marioni, R.E.* ; Hedman, A.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.* ; 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, S.* ; Sandling, J.H.* ; Stolk, L.* ; Uitterlinden, A.G.* ; Yet, I.* ; Castillo-Fernandez, J.E.* ; Spector, T.D.* ; Schwartz, J.D.* ; Vokonas, P.* ; Lind, L.* ; 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, E.* ; Levy, D.*

A DNA methylation biomarker of alcohol consumption.

Mol. Psychiatry 23, 422-433 (2018)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Gaba(b) Receptor; Disease; Dependence; Burden; Metaanalysis; Association; Microarray; Expression; Methylome; Body
ISSN (print) / ISBN 1359-4184
e-ISSN 1476-5578
Zeitschrift Molecular Psychiatry
Quellenangaben Band: 23, Heft: 2, Seiten: 422-433 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)