Prediction of antipsychotics efficacy based on a polygenic risk score: a real-world cohort study
Background: 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)...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1274442/full |
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| author | Marco De Pieri Marco De Pieri Marco De Pieri Marco De Pieri Marco Ferrari Giorgio Pistis Franziska Gamma Franca Marino Armin Von Gunten Philippe Conus Marco Cosentino Chin-Bin Eap Chin-Bin Eap Chin-Bin Eap Chin-Bin Eap |
| author_facet | Marco De Pieri Marco De Pieri Marco De Pieri Marco De Pieri Marco Ferrari Giorgio Pistis Franziska Gamma Franca Marino Armin Von Gunten Philippe Conus Marco Cosentino Chin-Bin Eap Chin-Bin Eap Chin-Bin Eap Chin-Bin Eap |
| author_sort | Marco De Pieri |
| collection | DOAJ |
| description | Background: 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.Materials and methods: We studied the association between a PRS composed of SNPs associated with response to antipsychotics in GWAS studies (PRSresponse) 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 (PRSschizophrenia1 and PRSschizophrenia2) were also tested for their association with response to treatment.Results: PRSresponse was significantly associated with response to antipsychotics considering the whole cohort (OR = 1.14, CI = 1.03–1.26, p = 0.010), the subgroup of patients with schizophrenia, schizoaffective disorder or bipolar disorder (OR = 1.18, CI = 1.02–1.37, p = 0.022, N = 235), with schizophrenia or schizoaffective disorder (OR = 1.24, CI = 1.04–1.47, p = 0.01, N = 176) and with schizophrenia (OR = 1.27, CI = 1.04–1.55, p = 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). PRSschizophrenia1 and PRSschizophrenia2 were not significantly associated with response to treatment.Conclusion: PRSresponse 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. |
| first_indexed | 2024-04-25T01:38:00Z |
| format | Article |
| id | doaj.art-b739dc4fb64044669dd3fc7822576771 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-25T01:38:00Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-b739dc4fb64044669dd3fc78225767712024-03-08T08:43:25ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-03-011510.3389/fphar.2024.12744421274442Prediction of antipsychotics efficacy based on a polygenic risk score: a real-world cohort studyMarco De Pieri0Marco De Pieri1Marco De Pieri2Marco De Pieri3Marco Ferrari4Giorgio Pistis5Franziska Gamma6Franca Marino7Armin Von Gunten8Philippe Conus9Marco Cosentino10Chin-Bin Eap11Chin-Bin Eap12Chin-Bin Eap13Chin-Bin Eap14Center for Research in Medical Pharmacology, Varese, ItalyPhD Program in Clinical and Experimental Medicine and Medical Humanities, University of Insubria, Varese, ItalyGeneral Psychiatry Service, Hopitaux Universitaires de Genève, Geneva, SwitzerlandUnit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Prilly, SwitzerlandCenter for Research in Medical Pharmacology, Varese, ItalyService of General Psychiatry, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Prilly, SwitzerlandLes Toises Psychiatry and Psychotherapy Center, Lausanne, SwitzerlandCenter for Research in Medical Pharmacology, Varese, ItalyService of Old Age Psychiatry, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Prilly, SwitzerlandService of General Psychiatry, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Prilly, SwitzerlandCenter for Research in Medical Pharmacology, Varese, ItalyUnit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Prilly, SwitzerlandSchool of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, SwitzerlandCenter for Research and Innovation in Clinical Pharmaceutical Sciences, University of Lausanne, Lausanne, Switzerland0Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, University of Lausanne, Lausanne, SwitzerlandBackground: 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.Materials and methods: We studied the association between a PRS composed of SNPs associated with response to antipsychotics in GWAS studies (PRSresponse) 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 (PRSschizophrenia1 and PRSschizophrenia2) were also tested for their association with response to treatment.Results: PRSresponse was significantly associated with response to antipsychotics considering the whole cohort (OR = 1.14, CI = 1.03–1.26, p = 0.010), the subgroup of patients with schizophrenia, schizoaffective disorder or bipolar disorder (OR = 1.18, CI = 1.02–1.37, p = 0.022, N = 235), with schizophrenia or schizoaffective disorder (OR = 1.24, CI = 1.04–1.47, p = 0.01, N = 176) and with schizophrenia (OR = 1.27, CI = 1.04–1.55, p = 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). PRSschizophrenia1 and PRSschizophrenia2 were not significantly associated with response to treatment.Conclusion: PRSresponse 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.https://www.frontiersin.org/articles/10.3389/fphar.2024.1274442/fullantipsychoticspersonalized medicineGWASresponse to treatmentpolygenic risk scoresingle nucleotide polimorphism (SNP) |
| spellingShingle | Marco De Pieri Marco De Pieri Marco De Pieri Marco De Pieri Marco Ferrari Giorgio Pistis Franziska Gamma Franca Marino Armin Von Gunten Philippe Conus Marco Cosentino Chin-Bin Eap Chin-Bin Eap Chin-Bin Eap Chin-Bin Eap Prediction of antipsychotics efficacy based on a polygenic risk score: a real-world cohort study Frontiers in Pharmacology antipsychotics personalized medicine GWAS response to treatment polygenic risk score single nucleotide polimorphism (SNP) |
| title | Prediction of antipsychotics efficacy based on a polygenic risk score: a real-world cohort study |
| title_full | Prediction of antipsychotics efficacy based on a polygenic risk score: a real-world cohort study |
| title_fullStr | Prediction of antipsychotics efficacy based on a polygenic risk score: a real-world cohort study |
| title_full_unstemmed | Prediction of antipsychotics efficacy based on a polygenic risk score: a real-world cohort study |
| title_short | Prediction of antipsychotics efficacy based on a polygenic risk score: a real-world cohort study |
| title_sort | prediction of antipsychotics efficacy based on a polygenic risk score a real world cohort study |
| topic | antipsychotics personalized medicine GWAS response to treatment polygenic risk score single nucleotide polimorphism (SNP) |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1274442/full |
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