As noted in our review of the literature, a number of human studies have supported altered DNA methylation in either the peripheral blood or postmortem brains of AUD subjects. However, it is unclear whether DNA methylation changes in AUD subjects result directly from alcohol consumption or predate the occurrence of alcohol abuse or dependence, and whether altered DNA methylation influences gene expression. It is already known that environmental factors such as early life stress and malnutrition (that may be abnormal in AUD subjects) can also alter DNA methylation patterns.99 Moreover, DNA methylation status in AUD subjects can be influenced by alcohol doses as well as co-occurring smoking, drug use, or comorbid psychiatric illness. To unravel the mechanisms underlying DNA methylation alterations observed in AUD subjects, at least four study approaches can be used.
