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Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis
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Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis
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Journal Article
Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis
2009
Overview
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.
Publisher
Springer International Publishing,Nature Publishing Group
Subject
/ Adult
/ Aged
/ Antipsychotic Agents - therapeutic use
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Clinical Trials as Topic - statistics & numerical data
/ Dopamine
/ Female
/ Fundamental and applied biological sciences. Psychology
/ General aspects. Genetic counseling
/ Genes
/ Genetics
/ Genetics of eukaryotes. Biological and molecular evolution
/ Genomes
/ GTP-Binding Proteins - genetics
/ Humans
/ Male
/ Molecular and cellular biology
/ Nerve Tissue Proteins - genetics
/ Patients
/ Polymorphism, Single Nucleotide
/ Schizophrenia - drug therapy
/ Studies
