Extensive genetic and genomic studies of the relationship between alcohol 
drinking preference and withdrawal severity have been performed using animal 
models. Data from multiple such publications and public data resources have been 
incorporated in the GeneWeaver database with >60,000 gene sets including 285 
alcohol withdrawal and preference-related gene sets. Among these are evidence 
for positional candidates regulating these behaviors in overlapping quantitative 
trait loci (QTL) mapped in distinct mouse populations. Combinatorial integration 
of functional genomics experimental results revealed a single QTL positional 
candidate gene in one of the loci common to both preference and withdrawal. 
Functional validation studies in Ap3m2 knockout mice confirmed these 
relationships. Genetic validation involves confirming the existence of 
segregating polymorphisms that could account for the phenotypic effect. By 
exploiting recent advances in mouse genotyping, sequence, epigenetics, and 
phylogeny resources, we confirmed that Ap3m2 resides in an appropriately 
segregating genomic region. We have demonstrated genetic and alcohol-induced 
regulation of Ap3m2 expression. Although sequence analysis revealed no 
polymorphisms in the Ap3m2-coding region that could account for all phenotypic 
differences, there are several upstream SNPs that could. We have identified one 
of these to be an H3K4me3 site that exhibits strain differences in methylation. 
Thus, by making cross-species functional genomics readily computable we 
identified a common QTL candidate for two related bio-behavioral processes via 
functional evidence and demonstrate sufficiency of the genetic locus as a source 
of variation underlying two traits.