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 & 53 others 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 journalArticle

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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.

LanguageEnglish (US)
Pages422-433
Number of pages12
JournalMolecular Psychiatry
Volume23
Issue number2
DOIs
StatePublished - Feb 1 2018

Fingerprint

DNA Methylation
Alcohol Drinking
Biomarkers
Alcohols
Methylation
GABA Receptors
Meta-Analysis
Monocytes
Neurotransmitter Receptor
DNA
Hispanic Americans
Routine Diagnostic Tests
Epigenomics
Genes
Area Under Curve
Phosphates
Population

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Liu, C., Marioni, R. E., Hedman, A. K., Pfeiffer, L., Tsai, P. C., Reynolds, L. M., ... Levy, D. (2018). A DNA methylation biomarker of alcohol consumption. Molecular Psychiatry, 23(2), 422-433. DOI: 10.1038/mp.2016.192

A DNA methylation biomarker of alcohol consumption. / 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. 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.

In: Molecular Psychiatry, Vol. 23, No. 2, 01.02.2018, p. 422-433.

Research output: Contribution to journalArticle

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. DOI: 10.1038/mp.2016.192
Liu C, Marioni RE, Hedman AK, Pfeiffer L, Tsai PC, Reynolds LM et al. A DNA methylation biomarker of alcohol consumption. Molecular Psychiatry. 2018 Feb 1;23(2):422-433. Available from, DOI: 10.1038/mp.2016.192
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. 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. In: Molecular Psychiatry. 2018 ; Vol. 23, No. 2. pp. 422-433
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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<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.",
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",
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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 (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.

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<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.

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