The 465 nominally significant genes mapped to sixty-seven pathways (Supplemental Table S5). Cholesterol biosynthesis was one of the most significant, with lower expression of HMGCR, CYP51A1 and IDI1. Chronic ethanol exposure has been shown to decrease cholesterol synthesis with an associated decrease in myelination in humans (Liu et al., 2006, McClintick et al., 2013) and animals (Alfonso-Loeches et al., 2012; McClintick et al., 2013; Pascual et al., 2014), leading to losses in white matter in the brain (Jacobus & Tapert, 2013). Upstream analysis was consistent with higher activity of TP53, TNF, LPS, TLRs, interferons and interleukins (Supplemental Table S6). In contrast to the effects of ethanol treatment, the analysis indicates Phospholipase C has higher activity in alcoholics.
