Prediction of antipsychotics efficacy based on a polygenic risk score: a real-world cohort study

• Published in: Frontiers in pharmacology 2024, Vol.15, p.1274442-1274442
• Main Authors: De Pieri, Marco, Ferrari, Marco, Pistis, Giorgio, Gamma, Franziska, Marino, Franca, Von Gunten, Armin, Conus, Philippe, Cosentino, Marco, Eap, Chin-Bin
• Format: Article
• Language: English
• Subjects: antipsychotics; GWAS; personalized medicine; polygenic risk score; response to treatment; single nucleotide polimorphism (SNP)
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2024.1274442

Response to antipsychotics is subject to a wide interindividual variability, due to genetic and non-genetic factors. Several single nucleotide polymorphisms (SNPs) have been associated with response to antipsychotics in genome-wide association studies (GWAS). Polygenic risk scores (PRS) are a powerful tool to aggregate into a single measure the small effects of multiple risk alleles. We studied the association between a PRS composed of SNPs associated with response to antipsychotics in GWAS studies (PRS ) in a real-world sample of patients (N = 460) with different diagnoses (schizophrenia spectrum, bipolar, depressive, neurocognitive, substance use disorders and miscellaneous). Two other PRSs composed of SNPs previously associated with risk of schizophrenia (PRS and PRS ) were also tested for their association with response to treatment. PRS was significantly associated with response to antipsychotics considering the whole cohort (OR = 1.14, CI = 1.03-1.26, = 0.010), the subgroup of patients with schizophrenia, schizoaffective disorder or bipolar disorder (OR = 1.18, CI = 1.02-1.37, = 0.022, N = 235), with schizophrenia or schizoaffective disorder (OR = 1.24, CI = 1.04-1.47, = 0.01, N = 176) and with schizophrenia (OR = 1.27, CI = 1.04-1.55, = 0.01, N = 149). Sensitivity and specificity were sub-optimal (schizophrenia 62%, 61%; schizophrenia spectrum 56%, 55%; schizophrenia spectrum plus bipolar disorder 60%, 56%; all patients 63%, 58%, respectively). PRS and PRS were not significantly associated with response to treatment. PRS defined from GWAS studies is significantly associated with response to antipsychotics in a real-world cohort; however, the results of the sensitivity-specificity analysis preclude its use as a predictive tool in clinical practice.