Zhang and Gelernter11 review studies about the potential importance of DNA methylation as a potential risk factor for AUD, i.e., as an epigenetic mechanism possibly affecting CpG dinucleotides. Work in this area is just beginning, as both the technology to examine possible epigenetic changes and the experimental strategies used continue to evolve. As new chips are developed, better coverage of the genome will become available. Factors such as gender and ancestry may also play important roles in determining any epigenetic changes discovered. Zhang and Gelernter point to many methodological issues that remain to be addressed, e.g., do methylation changes result from chronic alcohol consumption or do they predate heavy alcohol use, is there tissue specificity for epigenetic changes, and are such epigenetic changes specific to AUD or the result of other co-morbid psychiatric disorders, including other substance use disorders? It is not clear how important studies using model organisms will be as many genomic regions of interest are not well conserved across species. The methodological issues that have plagued the discovery of ‘risk’ genes for AUD are also the nemesis
