Alcohol and the methylome: design and analysis considerations for research using human samples.

BACKGROUND: A growing number of studies in human samples have sought to determine whether chronic alcohol use and alcohol use disorders (AUDs) may be associated with epigenetic factors, such as DNA methylation. We review the extant literature in light of some of the challenges that currently affect the design and interpretation of epigenetic research in human samples.
METHOD: A literature search was used to identify studies that have examined DNA methylation in relation to alcohol use or AUDs in human samples (through July 2013). A total of 22 studies were identified.
RESULTS: Associations with quantitative or diagnostic phenotypes of alcohol use or AUDs have been reported for several genes. However, all studies to date have relied on relatively small samples and cross-sectional study designs. Additionally, attempts to replicate results have been rare. More generally, research progress is hampered by several issues, including limitations of the technologies used to assess DNA methylation, tissue- and cell-specificity of methylation patterns, the difficulties of relating observed methylation differences at a given locus to a functional effect, and limited knowledge about the molecular mechanisms underlying the effects of alcohol on DNA methylation.
CONCLUSIONS: Although we share the optimism that epigenetics may lead to new insights into the etiology and pathophysiology of AUDs, the methodological and scientific challenges associated with conducting methylomic research in human samples need to be carefully considered when designing and evaluating such studies.