An Epigenomewide Association Study (EWAS) on Alcohol Consumption: A Monozygotic Twin Study

Alcohol consumption has been associated with many adverse health outcomes, but the mechanisms through which alcohol exerts its effect are not fully understood. Epigenetic mechanisms such as DNA methylation and resulting gene... [ view full abstract ]

Alcohol consumption has been associated with many adverse health outcomes, but the mechanisms through which alcohol exerts its effect are not fully understood. Epigenetic mechanisms such as DNA methylation and resulting gene expression may underlie this linkage. Here we conducted genomewide DNA methylation (using Illumina HumanMethylation450 BeadChip) and gene expression (by Illumina HumanHT-12 v4 Expression BeadChip) analysis using peripheral blood monocytes isolated from 47 monozygotic (MZ) twin pairs. A total of 392 CpG probes, clustered into 13 differentially methylated regions (DMRs), were found to be significantly associated with alcohol consumption. These regions included genes known to be related to alcohol drinking, e.g., GABBR1, GABARAP, GBX2, TDRD1, UNK, POLR3G and ZNF195. In addition, we identified 173 cis-and 288 trans-regulating genes associated with alcohol consumption. The identified alcohol-related DMR genes were enriched in GO terms such as alcohol oxidase activity, fatty alcohol metabolic process, and one-carbon metabolic process. Differential connectivity patterns in the co-methylation networks were also observed for genes involved in these three GO terms. Our results demonstrated that alcohol consumption alters DNA methylation and gene expression, independent of genetic and other potential confounding factors. These findings provide novel insight into biological mechanism involved in alcohol use, and may also unravel novel epigenetic pathways through which alcohol drinking contributes to alcohol-related diseases.