Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis.
The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Phase 1 Schizophrenia trial compared the effectiveness of one typical and four atypical antipsychotic medications. Although trials such as CATIE present important opportunities for pharmacogenetics research, the very richness of the clinical data presents challenges for statistical interpretation, and in particular the risk that data mining will lead to false-positive discoveries. For this reason, it is both misleading and unhelpful to perpetuate the current practice of reporting association results for these trials one gene at a time, ignoring the fact that multiple gene-by-phenotype tests are being carried out on the same data set. On the other hand, suggestive associations in such trials may lead to new hypotheses that can be tested through both replication efforts and biological experimentation. The appropriate handling of these forms of data therefore requires dissemination of association statistics without undue emphasis on select findings. Here we attempt to illustrate this approach by presenting association statistics for 2769 polymorphisms in 118 candidate genes evaluated for 21 pharmacogenetic phenotypes. On current evidence it is impossible to know which of these associations may be real, although in total they form a valuable resource that is immediately available to the scientific community.
Need
Anna C
AC
Center for Human Genome Variation, Institute for Genome Sciences & Policy, Duke University, Durham, NC 27708, USA.
Keefe
Richard S E
RS
Ge
Dongliang
D
Grossman
Iris
I
Dickson
Sam
S
McEvoy
Joseph P
JP
Goldstein
David B
DB
D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D003071:Cognition / Q000187:drug effects; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D010349:Patient Compliance; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics; D012565:Schizophrenic Psychology; D013223:Statistics as Topic; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics
D014150:Antipsychotic Agents; D009419:Nerve Tissue Proteins; C491492:RIMS1 protein, human; D019204:GTP-Binding Proteins