We began with a meta-analysis of gene expression changes associated with genetic predisposition to high alcohol consumption in mice (based on the 24 hr two-bottle choice test) (Mulligan et al., 2006). Initial examination of this data set showed statistically significantly regulation of functional pathways related to immune/inflammatory responses, including IL-1, IL-2, IL-6, NF-kB, Toll-like receptor and TNF receptor 1 signaling pathways. We then compared functional groups and individual genes identified in mice with expression studies in rats with genetic predisposition to high alcohol consumption (Kimpel et al., 2007) and in human alcoholics (Liu et al., 2006, 2007; Flatscher-Bader et al., 2008), Examination of data from these four gene expression studies showed that a number of genes differentially expressed in each study could be classified into a functional category broadly defined as “immune/inflammatory/defense/stress response” and we chose this pathway for our validation study. We applied five criteria for selection of genes from this functional category: 1) Statistical differences in gene expression (individual gene or over-represented pathway) related to predisposition to alcohol consumption in mice (Mulligan et al., 2006); 2) Statistical differences
