A DNA methylation biomarker of alcohol consumption

C. Liu; R. E. Marioni; K. 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, K. 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. YaoM. 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

^*Corresponding author for this work

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

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-7. Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P-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.Molecular Psychiatry advance online publication, 15 November 2016; doi:10.1038/mp.2016.192.

Original language	English
Journal	Molecular Psychiatry
Early online date	15 Nov 2016
DOIs	https://doi.org/10.1038/mp.2016.192
Publication status	E-pub ahead of print - 15 Nov 2016

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10.1038/mp.2016.192

mp2016192aFinal published version, 1.29 MBLicence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

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Liu, C., Marioni, R. E., Hedman, K. 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. (2016). A DNA methylation biomarker of alcohol consumption. Molecular Psychiatry. Advance online publication. https://doi.org/10.1038/mp.2016.192

@article{919583aeaac84ce79fbe2cb9b298122e,

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 (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-7. Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P-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.Molecular Psychiatry advance online publication, 15 November 2016; doi:10.1038/mp.2016.192.",

author = "C. Liu and Marioni, {R. E.} and Hedman, {K. 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 = "2016",

month = nov,

day = "15",

doi = "10.1038/mp.2016.192",

language = "English",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Nature Publishing Group",

}

Liu, C, Marioni, RE, Hedman, KK, 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 2016, 'A DNA methylation biomarker of alcohol consumption', Molecular Psychiatry. 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, K. 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 - 2016/11/15

Y1 - 2016/11/15

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 (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-7. Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P-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.Molecular Psychiatry advance online publication, 15 November 2016; doi:10.1038/mp.2016.192.

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 (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-7. Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P-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.Molecular Psychiatry advance online publication, 15 November 2016; doi:10.1038/mp.2016.192.

UR - http://www.scopus.com/inward/record.url?scp=84995495524&partnerID=8YFLogxK

U2 - 10.1038/mp.2016.192

DO - 10.1038/mp.2016.192

M3 - Article

AN - SCOPUS:84995495524

SN - 1359-4184

JO - Molecular Psychiatry

JF - Molecular Psychiatry

ER -

A DNA methylation biomarker of alcohol consumption

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A DNA methylation biomarker of alcohol consumption

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