residing in the lower quartile (t(88)=4.56, P = 1.65 e-05) (Fig. 2b). This correlation structure implies coherent biological function for a set of modules, comprising 2,330 genes in PFC, directly related to alcohol drinking behavior in humans. GMs within the upper quartile form two distinct groups (Group1: GM31, GM15, GM25, GM20 and Group2: GM19, GM30, GM33, GM28, GM13, GM37s), whereas GMs within the lower quartile share almost no pronounced inter-relationship. Interestingly, there was a significant difference for the average connectivity of genes residing in the upper versus the lower quartile and disease state (Fig. 2c). The interconnectedness of genes belonging to GMs weakly tied to alcohol consumption (i.e. lower quartile) followed a similar pattern to global differences in transcriptome organization between control and alcoholic PFC (Fig. 1b), while those within GMs linked with alcohol consumption (i.e. upper quartile) showed the reverse, with higher average gene connectivity in alcoholics compared to matched controls (F(1,14964)=111.5, P < 1e-16). This suggests a subtle restructuring of the transcriptome in alcoholic PFC favoring GMs associated with an individual’s lifelong pattern of alcohol intake. Due to the unique composition of gene networks associated with lifetime consumption of alcohol, gene coexpression in the upper quartile is less
