Journal
MOLECULAR PSYCHIATRY
Volume 23, Issue 2, Pages 422-433Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2016.192
Keywords
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Funding
- Biotechnology and Biological Sciences Research Council Funding Source: Medline
- Cancer Research UK [C864/A8257, 14136] Funding Source: Medline
- Intramural NIH HHS [Z99 HL999999] Funding Source: Medline
- Medical Research Council [MR/N003284/1, MC_UU_12015/1, MR/K026992/1, G0701120, G1000143, MR/L00002/1, MC_UU_12015/2, G1001245, G0401527, G9502233, MR/M013111/1] Funding Source: Medline
- NCATS NIH HHS [UL1 TR001079, UL1 TR001881, UL1 TR000124, UL1 TR000454, UL1 TR000040] Funding Source: Medline
- NHGRI NIH HHS [R01 HG006292] Funding Source: Medline
- NHLBI NIH HHS [R01 HL101250, R01 HL092111, N01HC95168, HHSN268201100011C, N01HC95162, N01HC85082, R01 HL105756, N01HC95165, N01HC55222, R01 HL111089, N01HC85079, N01HC95167, N01HC85083, N01HC95163, R01 HL087652, N01HC95166, HHSN268201100008C, N01HC95159, HHSN268201100006C, HHSN268200800007C, HHSN268201100012C, N01HC95164, N01HC85080, R01 HL116747, N01HC85081, HHSN268201100009C, HHSN268201100005C, N01HC25195, N01HC95169, U01 HL080295, R01 HL103612, R01 HL129132, HHSN268201100010C, K99 HL136875, RC2 HL102419, N01HC85086, N01HC95160, HHSN268201200036C, R01 HL120393, HHSN268201100007C, N01HC95161] Funding Source: Medline
- NIAAA NIH HHS [R21 AA027450] Funding Source: Medline
- NIA NIH HHS [R01 AG023629] Funding Source: Medline
- NIEHS NIH HHS [R01 ES021733, R01 ES015172] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
- ESRC [ES/N000404/1] Funding Source: UKRI
- MRC [MR/N003284/1, MC_U106179472, MC_UU_12015/1, MC_UU_12015/2] Funding Source: UKRI
- Economic and Social Research Council [ES/N000404/1] Funding Source: researchfish
- Medical Research Council [MR/L00002/1, G1001245, MR/K026992/1, G0701120, MC_U106179472, MR/M013111/1, MC_UU_12015/2, MC_UU_12015/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0514-10027] Funding Source: researchfish
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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 x 10(-7). Analysis of the monocyte-derived DNA (n = 1251) identified 62 alcohol-related CpGs at P < 1 x 10(-7). In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the gamma-Aminobutyric acid-A receptor delta and gamma-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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