A risk score based upon four SNPs selected from a set of eight dopaminergic genes in an initial training sample significantly predicted cocaine dependence symptoms in a replication testing sample. We would expect a large number of genetic variants, each with relatively small effect sizes, to substantially impact complex, continuous phenotypes only when considered in the aggregate (e.g., Plomin et al., 2009). Because there is potential for a large number of variants each with small effects, it could greatly benefit researchers to attempt aggregate replication of promising individual variants, especially in cases where the recent trend of rapidly increasing sample sizes may be impractical (e.g., for phenotypes requiring time- or cost-intensive measurement or selected samples).
