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A DNA methylation biomarker of alcohol consumption.
- Liu, C (author)
- Marioni, R E (author)
- Hedman, Åsa K (author)
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- Pfeiffer, L (author)
- Tsai, P-C (author)
- Reynolds, L M (author)
- Just, A C (author)
- Duan, Q (author)
- Boer, C G (author)
- Tanaka, T (author)
- Elks, C E (author)
- Aslibekyan, S (author)
- Brody, J A (author)
- Kühnel, B (author)
- Herder, C (author)
- Almli, L M (author)
- Zhi, D (author)
- Wang, Y (author)
- Huan, T (author)
- Yao, C (author)
- Mendelson, M M (author)
- Joehanes, R (author)
- Liang, L (author)
- Love, S-A (author)
- Guan, W (author)
- Shah, S (author)
- McRae, A F (author)
- Kretschmer, A (author)
- Prokisch, H (author)
- Strauch, K (author)
- Peters, A (author)
- Visscher, P M (author)
- Wray, N R (author)
- Guo, X (author)
- Wiggins, K L (author)
- Smith, A K (author)
- Binder, E B (author)
- Ressler, K J (author)
- Irvin, M R (author)
- Absher, D M (author)
- Hernandez, D (author)
- Ferrucci, L (author)
- Bandinelli, S (author)
- Lohman, K (author)
- Ding, J (author)
- Trevisi, L (author)
- Gustafsson, Stefan (author)
- Sandling, Johanna K. (author)
- Stolk, L (author)
- Uitterlinden, A G (author)
- Yet, I (author)
- Castillo-Fernandez, J E (author)
- Spector, T D (author)
- Schwartz, J D (author)
- Vokonas, P (author)
- Lind, Lars (author)
- Li, Y (author)
- Fornage, M (author)
- Arnett, D K (author)
- Wareham, N J (author)
- Sotoodehnia, N (author)
- Ong, K K (author)
- van Meurs, J B J (author)
- Conneely, K N (author)
- Baccarelli, A A (author)
- Deary, I J (author)
- Bell, J T (author)
- North, K E (author)
- Liu, Y (author)
- Waldenberger, M (author)
- London, S J (author)
- Ingelsson, Erik 1975- (author)
- Levy, D (author)
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- 2018
- 2018
- English.
- In: Molecular Psychiatry. - 1359-4184. ; 23, 422-433
- swepub:Mat__t
Abstract
Subject headings
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- 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.
Subject headings
- Medical and Health Sciences (hsv)
- Basic Medicine (hsv)
- Other Basic Medicine (hsv)
- Medicin och hälsovetenskap (hsv)
- Medicinska och farmaceutiska grundvetenskaper (hsv)
- Annan medicinsk grundvetenskap (hsv)
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- By the author/editor
- Liu, C
- Marioni, R E
- Hedman, Åsa K
- Pfeiffer, L
- Tsai, P-C
- Reynolds, L M
- show more...
- 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, Stef ...
- Sandling, Johann ...
- Stolk, L
- Uitterlinden, A ...
- Yet, I
- Castillo-Fernand ...
- 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 ...
- Levy, D
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