Replication pharmacogenetics

These preliminary observations demonstrate the feasibility of applying pharmacogenetics from the start of clinical development and the potential to elucidate relevant hypotheses from a relatively small sample size, although the results require replication and validation. Testing these hypotheses will require confirmation in a larger patient population (i.e., from phase 11/111 studies), which should also enable an assessment of the magnitude of effect and attributable risk. 

Large GWAS studies will have the benefit of ultimately confirming these associations. While the CB1 association with addiction has not been fully replicated, the CB1 gene does seem to be associated with an endophenotype found in drug users [270]. In this context, the likely role of the CB1 variants as pharmacogenetic variants should not be ignored [281-284],... 

These methodological differences account, at least in part, for the lack of replication observed across pharmacogenetic studies of antipsychotic response. Despite the challenges of conducting genetic studies in this area, a number of variants have shown consistent association with antipsychotic metabolism and response (Table 3). 

In 2008, Katz and colleagues [42] extended the search for associations of greater pharmacogenetic interest, although they limited their study to associations with pharmacokinetic variation. They identified consistently replicated associations for at least one drug between gene variants and human... 

---