AUTHOR=De Pieri Marco , Ferrari Marco , Pistis Giorgio , Gamma Franziska , Marino Franca , Von Gunten Armin , Conus Philippe , Cosentino Marco , Eap Chin-Bin 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1274442

DOI=10.3389/fphar.2024.1274442

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Materials and methods:</bold> We studied the association between a PRS composed of SNPs associated with response to antipsychotics in GWAS studies (PRS<sub>response</sub>) 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<sub>schizophrenia1</sub> and PRS<sub>schizophrenia2</sub>) were also tested for their association with response to treatment.</p><p><bold>Results:</bold> PRS<sub>response</sub> was significantly associated with response to antipsychotics considering the whole cohort (OR = 1.14, CI = 1.03–1.26, <italic>p</italic> = 0.010), the subgroup of patients with schizophrenia, schizoaffective disorder or bipolar disorder (OR = 1.18, CI = 1.02–1.37, <italic>p</italic> = 0.022, N = 235), with schizophrenia or schizoaffective disorder (OR = 1.24, CI = 1.04–1.47, <italic>p</italic> = 0.01, N = 176) and with schizophrenia (OR = 1.27, CI = 1.04–1.55, <italic>p</italic> = 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<sub>schizophrenia1</sub> and PRS<sub>schizophrenia2</sub> were not significantly associated with response to treatment.</p><p><bold>Conclusion:</bold> PRS<sub>response</sub> 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.</p>