Timothy Ramsey, Mark D Brennan
Background: Pharmacogenetic markers of antipsychotic response have the potential to reduce trial and error prescribing, leading to better outcomes. GLP1R genetic variation has previously shown PGx potential. This study was intended to identify testable GLP1R PGx markers and replicate their impact across multiple cohorts and studies. Methods and Findings: This study assigned haplotypes and biomarker status to subjects treated with olanzapine (n=172) or risperidone (n=181) in two independent cohorts of the Clinical Trials of Antipsychotic Intervention Effectiveness (CATIE) and an additional independent clinical study of schizophrenia and bipolar disorder at Vanderbilit University (ID NCT00179062). In each cohort subjects were assigned biomarker positive or negative status GLR1P Antipsychotic Response Predictor (GARP 1 and 3 respectively) and evaluated for change in Positive and Negative Syndrome Scale from baseline. GARP 1 status predicted greater symptom reduction in olanzapine-treated subjects in both CATIE cohorts (p=0.007 and 0.02, combined p=0.0004) and Vanderbilt (p=0.03). GARP 3 status predicted poorer symptom reduction in risperidone-treated subjects in the combined CATIE cohort (p=0.01) and Vanderbilt (p=0.01). Conclusions: In this study, we refined previous results that identified two PGx markers (GARP 1 and GARP 3) that predicted response to olanzapine and risperidone in the CATIE trial. We then replicated these findings in an independent clinical trial PGx. These PGx markers offer physicians a potential tool for more effective antipsychotic selection.
