Epigenetics of alcohol use disorder—A review of recent advances in DNA methylation profiling

Abstract

Alcohol use disorder (AUD) is a major contributor to morbidity and mortality worldwide. Although there is a heritable component, the etiology of AUD is complex and can involve environmental exposures like trauma and can be associated with many different patterns of alcohol consumption. Epigenetic modifications, which can mediate the influence of genetic variants and environmental variables on gene expression, have emerged as an important area of AUD research. Over the past decade, the number of studies investigating AUD and DNA methylation, a form of epigenetic modification, has grown rapidly. Yet we are still far from understanding how DNA methylation contributes to or reflects aspects of AUD. In this paper, we reviewed studies of DNA methylation and AUD and discussed how the field has evolved. We found that global DNA and candidate DNA methylation studies did not produce replicable results. To assess whether findings of epigenome‐wide association studies (EWAS) were replicated, we aggregated significant findings across studies and identified 184 genes and 15 gene ontological pathways that were differentially methylated in at least two studies and four genes and three gene ontological pathways that were differentially methylated in three studies. These genes and pathways repeatedly found enrichment of immune processes, which is in line with recent developments suggesting that the immune system may be altered in AUD. Finally, we assess the current limitations of studies of DNA methylation and AUD and make recommendations on how to design future studies to resolve outstanding questions.

DNA Hypomethylation as a Potential Link between Excessive Alcohol Intake and Cardiometabolic Dysfunction in Morbidly Obese Adults

“…Therefore, excess alcohol intake is expected to induce aberrant DNA methylation patterns, mostly hypomethylation. However, a few studies investigated these patterns in circulating blood cells yielding inconsistent findings [ 35 , 36 , 37 , 38 , 39 ]. Moreover, it is unclear how these patterns relate to specific metabolic or vascular characteristics in underrepresented morbidly obese persons.…”

Is DNA methylation in the brain a mechanism of alcohol use disorder?

“…Multiple epigenetic mechanisms have been implicated in AUD etiology, including histone modifications, expression of non-coding RNAs (reviewed elsewhere, Ponomarev, 2013;Berkel and Pandey, 2017;Bourguet et al, 2018;Gowen et al, 2021;Longley et al, 2021;Rodriguez, 2021;Zhu et al, 2022) and DNA methylation.…”

Sex-Related Differences in Voluntary Alcohol Intake and mRNA Coding for Synucleins in the Brain of Adult Rats Prenatally Exposed to Alcohol

“…Alcohol use disorder (AUD) is a severe and etiologically complex disease associated with high morbidity and mortality rates. Although the development of alcohol dependence has a strong genetic component [ 1 ], there are a wide variety of environmental factors that impact the vulnerability to AUD through epigenetic modifications [ 2 ].…”