c) Identifying the clustered, nominally positive SNPs within the strongest positive support from several “replication” datasets: We next seek convergence between data from several “replicate” samples. We focus on samples that test the same underlying hypothesis (eg that common allelic variants contribute to genetic components of vulnerability to develop substance dependence). Some of these samples and their matched controls differ from each other on other bases (eg racial/ethnic background, primary substances of abuse). We thus use “replication” here in a restricted sense. Such a restricted use of “replication” allows us to reserve use of the term “generalization” to denote identification of genes whose pleiotropic influences are evident in studies of other heritable phenotypes that often co-occur with addictions (see below). Obviously, there is also an aspect of “generalization” when comparing data from a) polysubstance dependent vs control samples collected from individuals of two racial/ethnic backgrounds with b) methamphetamine- dependent vs control samples collected from individuals with a third racial/ethnic background (see below).
