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Polygenic Risk Score Can Predict Drug Effectiveness

Am J Psychiatry; ePub 2018 Nov 5; Zhang, et al

Patients with higher polygenic risk scores (PRS) for schizophrenia tended to have less improvement with antipsychotic drug treatment, a recent study found. Therefore, PRS burden may have potential utility as a prognostic biomarker. All study subjects (4 independent cohorts of patients with first-episode psychosis, n=510) received initial treatment with antipsychotic medication for first-episode psychosis, and all were genotyped on standard single-nucleotide polymorphism (SNP) arrays imputed to the 1000 Genomes Project reference panel. PRS was computed based on the results of the large-scale schizophrenia genome-wide association studies (GWAS) reported by the Psychiatric Genomics Consortium. Researchers found:

  • In the discovery cohort, higher PRS significantly predicted higher symptom scores at the 12-week follow-up (controlling for baseline symptoms, sex, age, and ethnicity).
  • Higher PRS significantly predicted greater post-treatment symptoms in the combined replication analysis and was individually significant in 2 of the 3 replication cohorts.
  • Across the 4 cohorts, PRS was significantly predictive of adjusted 12-week symptom scores.
  • Patients with low PRS were more likely to be treatment responders than patients with high PRS.

Zhang J-P, Robinson D, Yu J, et al. Schizophrenia polygenic risk score as a predictor of antipsychotic efficacy in first-episode psychosis. [Published online ahead of print November 5, 2018]. Am J Psychiatry. doi:10.1176/appi.ajp.2018.17121363.