Methylation of a CpG Site Near the ALDH1A2 Gene is Associated with Loss of Control Over Drinking and Related Phenotypes

Abstract

The pathophysiology of alcohol use disorders (AUDs) may be influenced by epigenetics processes such as DNA methylation, but the identification of DNA methylation patterns associated with AUDs has largely been limited to a handful of candidate genes. Participants were hazardous drinkers from the local community (n=309). All participants completed a baseline clinical interview in which they reported on their loss of control over drinking. A subsample participated in an ethanol (EtOH) infusion experiment (n=50). DNA was extracted from saliva samples and assayed on the Illumina Infinium HumanMethylation27 DNA Analysis BeadChip. We identified significant associations between loss of control over drinking and DNA methylation at multiple CpG sites. In follow-up analyses of one of our top results, a CpG site near the ALDH1A2 gene, we found that methylation was negatively associated with rate of intoxication and self-reported feelings of intoxication, consistent with the view that DNA methylation at ALDH1A2 may be associated with changes in alcohol metabolism. While these findings require replication, they provide evidence that DNA methylation at multiple CpG sites is associated with loss of control over drinking. It may be useful to examine DNA methylation patterns using several related phenotypes to establish the biological coherence of results and to help prioritize markers for further study.