As described in the Methods, we used the S-score algorithm for probe-level analysis of each strain's transcriptional response to ethanol, followed by Fisher's combined probability test. This approach favors genes that consistently responded to ethanol across numerous BXD strains, regardless of direction, rather than genes that exhibited large differences in only a small subset of strains. Analysis of microarray datasets for PFC, NAc and VMB identified 3,512 probe-sets, corresponding to 2,743 unique genes, that changed significantly with ethanol in at least one brain region (Table S1). While not meant as a direct comparison due to differences in strains or directionality, these gene lists contained over 40% of the genes previously identified as ethanol-responsive by Kerns et al. (2005), despite differences in microarray design, investigators and analysis methods. This analysis also expanded the “ethanol responsome” nearly 10-fold. VMB exhibited the largest transcriptional response to ethanol, while changes observed in PFC and NAc were of comparable magnitude (Figure 1a). The transcriptional response to ethanol within each brain region included both unique and shared gene components. Roughly 1/3 of significantly ethanol-responsive genes in
