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A DNA methylation biomarker of alcohol consumption.

TitleA DNA methylation biomarker of alcohol consumption.
Publication TypeJournal Article
Year of Publication2018
AuthorsLiu 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
Secondary AuthorsLevy D
JournalMol Psychiatry
Volume23
Issue2
Pagination422-433
Date Published2018 02
ISSN1476-5578
KeywordsAdult, African Continental Ancestry Group, Aged, Alcohol Drinking, Alcohol-Related Disorders, Biomarkers, CpG Islands, DNA Methylation, Epigenesis, Genetic, Ethanol, European Continental Ancestry Group, Female, Genome-Wide Association Study, Humans, Male, Middle Aged
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=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

DOI10.1038/mp.2016.192
Alternate JournalMol Psychiatry
PubMed ID27843151
PubMed Central IDPMC5575985
Grant ListHHSN268201100008C / HL / NHLBI NIH HHS / United States
/ WT_ / Wellcome Trust / United Kingdom
R01 AG023629 / AG / NIA NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
R01 HG006292 / HG / NHGRI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
R01 HL129132 / HL / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
G0401527 / MRC_ / Medical Research Council / United Kingdom
HHSN268201100011C / HL / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
C864/A8257 / CRUK_ / Cancer Research UK / United Kingdom
R01 HL092111 / HL / NHLBI NIH HHS / United States
/ BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
MR/M013111/1 / MRC_ / Medical Research Council / United Kingdom
R01 HL101250 / HL / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
G1001245 / MRC_ / Medical Research Council / United Kingdom
G9502233 / MRC_ / Medical Research Council / United Kingdom
N01HC85082 / HL / NHLBI NIH HHS / United States
MR/K026992/1 / MRC_ / Medical Research Council / United Kingdom
R01 ES015172 / ES / NIEHS NIH HHS / United States
MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom
R01 HL105756 / HL / NHLBI NIH HHS / United States
R01 ES021733 / ES / NIEHS NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
R01 HL111089 / HL / NHLBI NIH HHS / United States
UL1 TR000454 / TR / NCATS NIH HHS / United States
MC_UU_12015/2 / MRC_ / Medical Research Council / United Kingdom
N01HC85079 / HL / NHLBI NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
G0701120 / MRC_ / Medical Research Council / United Kingdom
MR/L00002/1 / MRC_ / Medical Research Council / United Kingdom
HHSN268201100005C / HL / NHLBI NIH HHS / United States
R21 AA027450 / AA / NIAAA NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
Z99 HL999999 / ImNIH / Intramural NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
R01 HL116747 / HL / NHLBI NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
K99 HL136875 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States