There is a strong correlation between the brain volume component and duration of drinking. A previously reported study (Pfefferbaum et al., 1998) demonstrated a significantly faster deterioration of brain tissue in alcohol dependent subjects than healthy controls. Similar gray matter and ventricle changes were also reported in Harper and Kril (1989), Jernigan et al. (1991), de la Monte (1988), Pfefferbaum et al. (1995). Another study (Bartzokis et al., 2000) demonstrated similar results in cocaine dependent subjects. In light of these results, it is not surprising that we also observed a strong connection between duration of drinking and brain volume variation associated with alcohol use disorder severity. However, after accounting for co-variation with duration of drinking, Fig. 7 the brain volume variations we observe still show a significant difference between deletion carriers, insertion carriers and subjects with no variation at chromosome 11 q14.2. This is consistent with our initial model, Fig. 1 which includes contributions to brain volume variation from both CNVs and alcohol dependent behavior. Duration of drinking is also highly correlated (0.44) with the alcohol use disorder severity component
