Human linkage analysis and genome-wide association studies are powerful tools for genetic analysis of drug and alcohol abuse (Agrawal et al. 2008, Uhl et al. 2008b). Mouse genetic analyses provide a complement to these studies by allowing access to genetic coregulation of molecular phenotypes in tissues that are not available in human clinical studies, and provide independent confirmation of regulatory loci by evaluating conservation of phenotypic association across studies (Belfer et al. 2006; Uhl et al. 2008a). Although positional candidacy is a requirement for genetic causality, our ultimate goal is to identify trait relevant genes, and therefore we include gene expression correlates. An important caveat to this approach is that the available gene expression data may come from tissues that are not necessarily the most relevant or complete substrate for the trait under consideration. These data should not be used as an exclusive filter for the candidates, but do show support for candidacy. All of the resulting genes may be candidates for human gene association studies (Saccone et al. 2009), because it is likely that it is the role of the gene in phenotypic variation and not the specific polymorphism that is conserved.
