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Epigenome‐Wide DNA Methylation Association Analysis Identified Novel Loci in Peripheral Cells for Alcohol Consumption Among European American Male Veterans
Author(s) -
Xu Ke,
MontalvoOrtiz Janitza L.,
Zhang Xinyu,
Southwick Steven M.,
Krystal John H.,
Pietrzak Robert H.,
Gelernter Joel
Publication year - 2019
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.14168
Subject(s) - dna methylation , cpg site , epigenome , methylation , biology , differentially methylated regions , genetics , medicine , gene , gene expression
Background Hazardous alcohol consumption has significant adverse medical consequences. These effects may be mediated, in part, by alterations in DNA methylation. Thus, DNA methylation signatures in peripheral cells may provide biomarkers of the medical impact of alcohol use and the risk for future alcohol consumption. Method Using a high‐density methylation array, we characterized epigenome‐wide DNA methylation in saliva cells with respect to alcohol consumption in a large cohort of male European American veterans. In this study, DNA methylation of over 870,000 CpG DNA sites was profiled in 1,135 European American men. Alcohol consumption was assessed using the Alcohol Use Disorder Identification Test‐Consumption ( AUDIT ‐C). Linear regression was applied in an epigenome‐wide association study ( EWAS ), adjusted for confounders. Gene set enrichment analysis was performed in the KEGG database with a correction for gene length. Results We found that a total of 70 CpG sites reached EWAS ‐corrected significance ( p < 6E‐08) with small effects on alcohol consumption for individual CpG sites, including 64 new CpG sites and 6 CpG sites that were previously reported as associated with alcohol use disorder, liver function, body mass index, and lipid metabolism. The most significant CpG site was located in SLC 7A11 ( t = −11.34, p = 2.66E‐28), a gene involved specifically in cysteine and glutamate transportation. The 70 significant CpG sites were located on 44 genes, including genes involved in amino acid transport and metabolism systems. We identified 68 pathways with a false discovery rate < 0.05. Conclusions We identified novel DNA methylation sites associated with alcohol consumption. Results may shed light on peripheral mechanisms of alcohol consumption on adverse health outcomes among heavy drinkers.