In the present study, we searched for replicable risk gene regions for alcohol and nicotine co-dependence in two distinct American populations using GWAS. In the association analysis, we separated European-Americans (EAs) and African-Americans (AAs) to increase population homogeneity, and controlled for admixture effects. The association findings from the EAs were replicated in the AAs and vice versa. Additionally, we used an independent sample with distinct tissues to detect expression quantitative trait locus (eQTL) signals, as a confirmation of the association findings. Furthermore, we applied a stringent definition of replication (see below). The primary target of investigation in the current study was not the top-ranked SNPs in the discovery sample as previous GWASs, but rather the replicable risk regions that might harbor the population-generalizable and functional variants. This strategy led to the discovery of novel risk loci for alcohol and nicotine co-dependence.
