To identify novel candidate genes involved in alcohol responses, we used gene set overlap analysis within the Ontological Discovery Environment (Baker et al., 2009) and the Ethanol-Related Gene Resource (Guo et al., 2009) to rank data from multiple microarray studies of ethanol-related genes in mouse (Kerns et al., 2005, Mulligan et al., 2006) and human alcoholic brain (Liu et al., 2006, Mayfield et al., 2002). The most highly ranked gene from our analyses, Chloride Intracellular Channel 4 (Clic4), was represented across six independent microarray, linkage and association studies. For example, our prior microarray studies showed that Clic4 had lower basal expression but greater ethanol-responsive expression in prefrontal cortex (PFC) of DBA/2J mice compared to C57BL/6 mice (Supplemental Figure S1; two-way ANOVA; treatment, F(1,12)=7.28, p=0.027; genotype, F(1,12)=8.082, p=0.022; interaction, F(1,12)=11.158, p=0.010, n=3); also see (Kerns et al., 2005)). These two mouse strains differ widely in terms of multiple behavioral responses to acute or chronic ethanol, as well as ethanol consumption (Metten et al., 1998). We also found that Clic4 was in other published datasets for genes associated with ethanol drinking preference
