A DNA methylation biomarker of alcohol consumption

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

doi:10.1038/mp.2016.192

A DNA methylation biomarker of alcohol consumption

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 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

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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.Molecular Psychiatry advance online publication, 15 November 2016; doi:10.1038/mp.2016.192.

Original language	English
Journal	Molecular Psychiatry
DOIs	https://doi.org/10.1038/mp.2016.192
Publication status	Published - 15 Nov 2016

Keywords

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/mp.2016.192Licence: CC BY-NC-ND

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Liu, C., Marioni, R. E., Hedman, Å. 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. https://doi.org/10.1038/mp.2016.192

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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.Molecular Psychiatry advance online publication, 15 November 2016; doi:10.1038/mp.2016.192.",

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doi = "10.1038/mp.2016.192",

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Liu, C, Marioni, RE, Hedman, ÅK, Pfeiffer, L, Tsai, P-C, 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, S-A, 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, Å 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<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.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<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.Molecular Psychiatry advance online publication, 15 November 2016; doi:10.1038/mp.2016.192.

KW - Journal Article

U2 - 10.1038/mp.2016.192

DO - 10.1038/mp.2016.192

M3 - Article

C2 - 27843151

SN - 1359-4184

JO - Molecular Psychiatry

JF - Molecular Psychiatry

ER -

A DNA methylation biomarker of alcohol consumption

Abstract

Keywords

UN SDGs

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