McClintick and colleagues 11 conducted an RNA sequencing study in which LCLs from COGA participants were treated with 75 mM ethanol for 48 h. Ethanol affected expression of 4456 of the 12,503 genes detectably expressed (at an FDR ≤ 0.05). Cells from individuals with and without AUD responded similarly to ethanol, although expression of genes in the cholesterol biosynthesis pathway, including the one encoding the rate‐limiting enzyme HMGCR, was lower in participants with AUD. The affected genes fell into many pathways, including activation of NF‐κB, neuroinflammation, IL6, IL2, IL8, and dendritic cell maturation pathways, consistent with increased signaling by NF‐κB, TNF, IL1, IL4, IL18, TLR4, and LPS. Signaling by interferons A and B decreased, as did EIF2 signaling, phospholipase C signaling, and glycolysis. 11
