A DNA methylation biomarker of alcohol consumption View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-02

AUTHORS

C Liu, R E Marioni, Å K Hedman, L Pfeiffer, P-C Tsai, L M Reynolds, A C Just, Q Duan, C G Boer, T Tanaka, C E Elks, S Aslibekyan, J A Brody, B Kühnel, C Herder, L M Almli, D Zhi, Y Wang, T Huan, C Yao, M M Mendelson, R Joehanes, L Liang, S-A Love, W Guan, S Shah, A F McRae, A Kretschmer, H Prokisch, K Strauch, A Peters, P M Visscher, N R Wray, X Guo, K L Wiggins, A K Smith, E B Binder, K J Ressler, M R Irvin, D M Absher, D Hernandez, L Ferrucci, S Bandinelli, K Lohman, J Ding, L Trevisi, S Gustafsson, J H Sandling, L Stolk, A G Uitterlinden, I Yet, J E Castillo-Fernandez, T D Spector, J D Schwartz, P Vokonas, L Lind, Y Li, M Fornage, D K Arnett, N J Wareham, N Sotoodehnia, K K Ong, J B J van Meurs, K N Conneely, A A Baccarelli, I J Deary, J T Bell, K E North, Y Liu, M Waldenberger, S J London, E Ingelsson, D Levy

ABSTRACT

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. More... »

PAGES

422

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/mp.2016.192

DOI

http://dx.doi.org/10.1038/mp.2016.192

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1047722630

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27843151


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