Archival ReportIdentification of Novel Candidate Genes for Treatment Response to Risperidone and Susceptibility for Schizophrenia: Integrated Analysis Among Pharmacogenomics, Mouse Expression, and Genetic Case-Control Association Approaches
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Subjects and Collection of Clinical Data
We performed an open-labeled pharmacogenetic study involving 108 first-episode, previously antipsychotic-naive schizophrenic patients. All received risperidone monotherapy after enrollment. Details are described elsewhere (6, 7). Briefly, patients were entered into the study if they 1) met DSM-IV-TR criteria for schizophrenia (and then remained in follow-up to at least 6 months), 2) were physically healthy and had all laboratory parameters within normal limits, and 3) had neither a current nor
Possible Predictor SNPs for Risperidone Treatment: From Pharmacogenomic Result (Study 1)
Among the 62,935 SNPs we examined in the pharmacogenomics study, 51,550 SNPs were annotated to 14,655 genes (annotation span: 5′ or 3′ ± 20 kb). For a number of genes, we had multiple SNPs with p values less than 5.0 × 10−4 because of the high LD among genotyped markers. Where this occurred, we list only the strongest associated SNP from that gene (the top 10 hits and SNPs with p value less than 5.0 × 10−4 in Table 1 and Table S1 in Supplement 1, respectively).
We also looked specifically in our
Combined Analysis as a Tool for Prioritizing Candidate Genes for Pharmacogenomics and Susceptibility
Genomewide approaches to pharmacogenomics have the capacity to provide novel insights into mechanisms and predictors of drug response. However, a major concern of this approach, which is not specific to pharmacogenomics, relates to balancing the need to set a stringent threshold for the type I error rate against the desire to achieve power to detect findings at that threshold. Unless the genetic effect sizes in pharmacogenetics are substantially greater than is typical for complex diseases (19
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