Transcriptome-wide analysis of expression in LCLs from AD and controls may aid the interpretation of variants identified by genetic association studies. Treatment of LCLs with ethanol can reveal direct, relatively short-term effects on cellular function. In a previous microarray study, we examined the effects of 24 h exposure to 75 mM ethanol, which was not toxic to the cells, in LCLs from 21 individuals who met DSM-IV criteria for alcohol dependence and 21 controls (McClintick et al., 2014). The individuals from whom LCLs were created were carefully diagnosed as part of the Collaborative Study on the Genetics of Alcoholism (COGA) (Begleiter et al., 1995). Nearly half of all the expressed genes were affected by ethanol, but most changes were very small; fewer than 20% had absolute fold changes >1.2. Pathways affected included increased pro-inflammatory pathways including IL6, dendritic cell maturation, TNF and NFκB, and a decrease in the anti-inflammatory IL10 pathway. Analysis indicated that NFκB, IL6, TNF and other cytokines were likely active, along with TLRs and interferons (McClintick et al., 2014). There was limited power to detect differences between untreated AD and controls, but decreased IGF1 signaling and increases in protein ubiquitination and hypoxia signaling were identified.
