The last study by Philibert and colleagues [101] was designed to overcome limitations of some of the above studies. Specifically, instead of looking at the trait of alcohol dependence in the presence or absence of recent alcohol use, it purposively selected active, heavy alcohol consumers entering and exiting treatment for alcohol use disorders versus community controls who were selected from an environment in which alcohol use was discouraged whose self-reports were confirmed by objective biomarkers for smoking and cannabis use. Methylation signatures on treatment entry were compared with those of controls and with those of the same alcohol-dependent individuals at 4 weeks following treatment entry. Although significant changes within individuals in the four weeks following treatment entry were not detected, 8626 probes were found to be differentially methylated between cases and controls after conservative Bonferroni correction, with top delta beta values generally less than 10%. Of note, the largest delta beta of approximately 15% was seen for GFI1, a gene reported in a number of smoking studies (see above), suggesting possible confounding at this locus.
