on a diagnosis of substance dependence was not a requirement for cases because of the significant co-morbidity between alcohol and substance dependence. Several analyses were performed with the European American case-control GWAS being the primary analysis. Although no genome-wide significant SNPs (p < 10–8) were reported in the primary analysis, combined evidence from the case-control GWAS, a family-based replication study and differential gene expression analysis converged on a cluster of genes on chromosome 11 with the strongest evidence of association. These genes included SNPs within or near: SLC22A18, PHLDA2, NAP1L4, SNORA54, CARS, and OSBPL5. Below we describe the potential functional significance of two of these genes, CARS and NAP1L4, because of possible relevance to one or more addiction cycle domains (Fig. 1 and Table 3).
