A DNA methylation biomarker of alcohol consumption

C. Liu; R. E. Marioni; A. 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

doi:10.1038/mp.2016.192

A DNA methylation biomarker of alcohol consumption

C. Liu
, R. E. Marioni
, A. 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

Research output: Contribution to journal › Article › peer-review

297 Scopus citations

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 (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<1×10 ^-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.

Original language	English
Pages (from-to)	422-433
Number of pages	12
Journal	Molecular Psychiatry
Volume	23
Issue number	2
DOIs	https://doi.org/10.1038/mp.2016.192
State	Published - 1 Feb 2018
Externally published	Yes

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10.1038/mp.2016.192

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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., ... Levy, D. (2018). A DNA methylation biomarker of alcohol consumption. Molecular Psychiatry, 23(2), 422-433. https://doi.org/10.1038/mp.2016.192

@article{9be55b04b6a249c5a04d2684eebac714,

title = "A DNA methylation biomarker of alcohol consumption",

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 (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{\texttimes}10 -7 . Analysis of the monocyte-derived DNA (n = 1251) identified 62 alcohol-related CpGs at P<1{\texttimes}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.",

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

year = "2018",

month = feb,

day = "1",

doi = "10.1038/mp.2016.192",

language = "English",

volume = "23",

pages = "422--433",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Springer Nature",

number = "2",

}

Liu, C, Marioni, RE, Hedman, AK, Pfeiffer, L, Tsai, PC, 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, SA, 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 2018, 'A DNA methylation biomarker of alcohol consumption', Molecular Psychiatry, vol. 23, no. 2, pp. 422-433. https://doi.org/10.1038/mp.2016.192

TY - JOUR

T1 - A DNA methylation biomarker of alcohol consumption

AU - Liu, C.

AU - Marioni, R. E.

AU - Hedman, A. K.

AU - Pfeiffer, L.

AU - Tsai, P. C.

AU - Reynolds, L. M.

AU - Just, A. C.

AU - Duan, Q.

AU - Boer, C. G.

AU - Tanaka, T.

AU - Elks, C. E.

AU - Aslibekyan, S.

AU - Brody, J. A.

AU - Kühnel, B.

AU - Herder, C.

AU - Almli, L. M.

AU - Zhi, D.

AU - Wang, Y.

AU - Huan, T.

AU - Yao, C.

AU - Mendelson, M. M.

AU - Joehanes, R.

AU - Liang, L.

AU - Love, S. A.

AU - Guan, W.

AU - Shah, S.

AU - McRae, A. F.

AU - Kretschmer, A.

AU - Prokisch, H.

AU - Strauch, K.

AU - Peters, A.

AU - Visscher, P. M.

AU - Wray, N. R.

AU - Guo, X.

AU - Wiggins, K. L.

AU - Smith, A. K.

AU - Binder, E. B.

AU - Ressler, K. J.

AU - Irvin, M. R.

AU - Absher, D. M.

AU - Hernandez, D.

AU - Ferrucci, L.

AU - Bandinelli, S.

AU - Lohman, K.

AU - Ding, J.

AU - Trevisi, L.

AU - Gustafsson, S.

AU - Sandling, J. H.

AU - Stolk, L.

AU - Uitterlinden, A. G.

AU - Yet, I.

AU - Castillo-Fernandez, J. E.

AU - Spector, T. D.

AU - Schwartz, J. D.

AU - Vokonas, P.

AU - Lind, L.

AU - Li, Y.

AU - Fornage, M.

AU - Arnett, D. K.

AU - Wareham, N. J.

AU - Sotoodehnia, N.

AU - Ong, K. K.

AU - Van Meurs, J. B.J.

AU - Conneely, K. N.

AU - Baccarelli, A. A.

AU - Deary, I. J.

AU - Bell, J. T.

AU - North, K. E.

AU - Liu, Y.

AU - Waldenberger, M.

AU - London, S. J.

AU - Ingelsson, E.

AU - Levy, D.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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<1×10 -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.

AB - 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<1×10 -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.

UR - https://www.scopus.com/pages/publications/84995495524

U2 - 10.1038/mp.2016.192

DO - 10.1038/mp.2016.192

M3 - Article

C2 - 27843151

AN - SCOPUS:84995495524

SN - 1359-4184

VL - 23

SP - 422

EP - 433

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 2

ER -

A DNA methylation biomarker of alcohol consumption

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