A DNA methylation biomarker of alcohol consumption
Open accessAbstract
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.
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- Authors
- 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., 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.
- Affiliations
- Boston University (US)
- The University of Queensland (AU)
- Uppsala University (SE)
- Helmholtz Munich (DE)
- King's College London (GB)
- Wake Forest University Health Sciences (US)
- Icahn School of Medicine at Mount Sinai (US)
- University of North Carolina at Chapel Hill (US)
- Erasmus MC (NL)
- National Institute on Aging (US)
- University of Cambridge (GB)
- University of Alabama at Birmingham (US)
- University of Washington (US)
- Deutsches Diabetes-Zentrum e.V. (DE)
- Emory University (US)
- The University of Texas Health Science Center at Houston (US)
- National Heart, Lung, and Blood Institute (US)
- Harvard University (US)
- University of Minnesota (US)
- Harbor–UCLA Medical Center (US)
- Max Planck Institute of Psychiatry (DE)
- McLean Hospital (US)
- HudsonAlpha Institute for Biotechnology (US)
- National Institutes of Health (US)
- Azienda Sanitaria di Firenze (IT)
- University of Kentucky (US)
- Columbia University (US)
- University of Edinburgh (GB)
- Corresponding author
- Liu, C
- Levy, D
- ORCID
- Liu, C
- Marioni, R E
- Hedman, Å K
- Reynolds, L M
- Just, A C
- Duan, Q
- Boer, C G
- Tanaka, T
- Aslibekyan, S
- Brody, J A
- Kühnel, B
- Herder, C
- Almli, L M
- Wang, Y
- Huan, T
- Yao, C
- Mendelson, M M
- Joehanes, R
- Liang, L
- Guan, W
- Shah, S
- McRae, A F
- 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
- Trevisi, L
- Gustafsson, S
- Uitterlinden, A G
- Yet, I
- Spector, T D
- Schwartz, J D
- Vokonas, P
- Lind, L
- Li, Y
- Fornage, M
- Arnett, D K
- Wareham, N J
- Ong, K K
- 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
- Venue
- Molecular Psychiatry
- Published
- 2016-11-15
- Volume
- 23
- Issue
- 2
- Pages
- 422-433
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC5575985
- OpenAlex
- W2552955852
- Cited by
- 402
- References
- 4
- Citations by year
- 2026: 22 · 2025: 32 · 2024: 46 · 2023: 32 · 2022: 86 · 2021: 57 · 2020: 48 · 2019: 32 · 2018: 29 · 2017: 18
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Psychiatry (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (acceptedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by-nc-nd)
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- RePub (Erasmus University Rotterdam) (submittedVersion)
- Funders
- Wellcome Trust
- Cancer Research UK (14136, C/864/A8257)
- National Institute for Health and Care Research (NF-SI-0512-10114, NF-SI-0514-10027)
- National Institutes of Health (n01hc95164-17-0-1, n01hc085082-026, n01hc085081-021, n01hc085079-024, 1r01hl120393-01a1, n01hc085083-027, n01hc95165-34-0-1, n01hc085080-026, n01hc95161-24-0-1, n01hc095169-003, UL1TR000124, n01hc95166-21-0-1, 5r01hl101250-05, n01hc085086-022, n01hc95162-31-0-1, Z99 HL999999, n01hc95168-27-0-1, n01hc95160-18-0-1, n01hc095167-000, UL1TR000454, UL1TR001079, n01hc25195-41-0-1, n01hc95163-22-0-1, n01hc55222-0-0-0, n01hc95159-40-0-1, UL1TR000040, UL1TR001881)
- Medical Research Council (MR/K026992/1, MC_UU_12015/2, MR/M013111/1, MR/N003284/1, MC_UU_12015/1)
- Biotechnology and Biological Sciences Research Council
- Economic and Social Research Council (ES/N000404/1)
- National Institute on Alcohol Abuse and Alcoholism (R21AA027450)
- National Institute on Aging (R01AG023629)
- National Heart, Lung, and Blood Institute (N01-HC-85081, HHSN268201 100012C, HHSN268201100007C, N01HC-85083, N01 HC-95159, N01-HC-95160, HHSN2682 01100008C, N01 HC-95168, HH-SN-268201100006C, HHSN268201100011C, N01 HC95167, (N01-HC-95163, K99HL136875, R01-HL120393, R01HL116747, N01‐HC25195, N01HC85082, N01 HC85086, N01 HC-95161, N01 HC95165, N01HC95164, R01-HL-101250, R01HL087652, HHSN268201100005C, R01HL103612, HHSN 268200800007C, N01HC85080, HHSN268201100010C, R01HL111089, N01 HC55222, R01HL129132, HHSN268201200036C, HHSN26820 1100009C, R01HL105756, U01HL080295, N01‐HC‐95166, N01 HC-95162, R01HL092111, RC2HL102419, N01-HC85079, N01 HC95169)
- National Human Genome Research Institute (R01HG006292)
- National Institute of Environmental Health Sciences (R01ES021733, R01ES015172)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- DNA methylation, alcohol consumption, alcohol biomarkers, heavy drinking, epigenome-wide association study, CpG sites, neurotransmitter receptors, immune function genes, whole blood, alcohol-related disorders
- MeSH terms
- Adult, Aged, Alcohol Drinking, Ethanol, Female, Humans, Male, Middle Aged, Biomarkers, CpG Islands, DNA Methylation, Alcohol-Related Disorders, Epigenesis, Genetic, Black People, White People, Genome-Wide Association Study
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