Associations Between Polygenic Risk Score Loading, Psychosis Liability, and Clozapine Use Among Individuals With Schizophrenia.

Autor:	Lin BD; Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, the Netherlands.; Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, the Netherlands.; Department of Preventive Medicine, Institute of Biomedical Informatics, Bioinformatics Center, School of Basic Medical Sciences, Henan University, Kaifeng, China.; Department of Psychiatry, University Medical Center Utrecht, Utrecht University, Brain Center Rudolf Magnus, Utrecht, the Netherlands., Pinzón-Espinosa J; Department of Psychiatry, University Medical Center Utrecht, Utrecht University, Brain Center Rudolf Magnus, Utrecht, the Netherlands.; Sant Pau Mental Health Group, Institut d'Investigació Biomèdica Sant Pau (IBB-Sant Pau), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Barcelona, Catalonia, Spain.; Department of Medicine, School of Medicine, University of Barcelona, Barcelona, Spain.; Department of Clinical Psychiatry, School of Medicine, University of Panama, Panama City, Panama., Blouzard E; Department of Psychiatry, University Medical Center Utrecht, Utrecht University, Brain Center Rudolf Magnus, Utrecht, the Netherlands., van der Horst MZ; Department of Psychiatry, University Medical Center Utrecht, Utrecht University, Brain Center Rudolf Magnus, Utrecht, the Netherlands.; GGNet Mental Health, Warnsveld, the Netherlands., Okhuijsen-Pfeifer C; Department of Psychiatry, University Medical Center Utrecht, Utrecht University, Brain Center Rudolf Magnus, Utrecht, the Netherlands., van Eijk KR; Department of Psychiatry, University Medical Center Utrecht, Utrecht University, Brain Center Rudolf Magnus, Utrecht, the Netherlands., Guloksuz S; Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, the Netherlands.; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut., Peyrot WJ; Department of Psychiatry, Amsterdam UMC, Amsterdam, the Netherlands.; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands., Luykx JJ; Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, the Netherlands.; Research Institute Brainclinics, Brainclinics Foundation, Nijmegen, the Netherlands.; Department of Psychiatry, University Medical Center Utrecht, Utrecht University, Brain Center Rudolf Magnus, Utrecht, the Netherlands.; GGNet Mental Health, Warnsveld, the Netherlands.
Jazyk:	angličtina
Zdroj:	JAMA psychiatry [JAMA Psychiatry] 2023 Feb 01; Vol. 80 (2), pp. 181-185.
DOI:	10.1001/jamapsychiatry.2022.4234
Abstrakt:	Importance: Predictors consistently associated with psychosis liability and course of illness in schizophrenia (SCZ) spectrum disorders (SSD), including the need for clozapine treatment, are lacking. Longitudinally ascertained medication use may empower studies examining associations between polygenic risk scores (PRSs) and pharmacotherapy choices. Objective: To examine associations between PRS-SCZ loading and groups with different liabilities to SSD (individuals with SSD taking clozapine, individuals with SSD taking other antipsychotics, their parents and siblings, and unrelated healthy controls) and between PRS-SCZ and the likelihood of receiving a prescription of clozapine relative to other antipsychotics. Design, Setting, and Participants: This genetic association study was a multicenter, observational cohort study with 6 years of follow-up. Included were individuals diagnosed with SSD who were taking clozapine or other antipsychotics, their parents and siblings, and unrelated healthy controls. Data were collected from 2004 until 2021 and analyzed between October 2021 and September 2022. Exposures: Polygenic risk scores for SCZ. Main Outcomes and Measures: Multinomial logistic regression was used to examine possible differences between groups by computing risk ratios (RRs), ie, ratios of the probability of pertaining to a particular group divided by the probability of healthy control status. We also computed PRS-informed odd ratios (ORs) for clozapine use relative to other antipsychotics. Results: Polygenic risk scores for SCZ were generated for 2344 participants (mean [SD] age, 36.95 years [14.38]; 994 female individuals [42.4%]) who remained after quality control screening (557 individuals with SSD taking clozapine, 350 individuals with SSD taking other antipsychotics during the 6-year follow-up, 542 parents and 574 siblings of individuals with SSD, and 321 unrelated healthy controls). All RRs were significantly different from 1; RRs were highest for individuals with SSD taking clozapine (RR, 3.24; 95% CI, 2.76-3.81; P = 2.47 × 10-46), followed by individuals with SSD taking other antipsychotics (RR, 2.30; 95% CI, 1.95-2.72; P = 3.77 × 10-22), parents (RR, 1.44; 95% CI, 1.25-1.68; P = 1.76 × 10-6), and siblings (RR, 1.40; 95% CI, 1.21-1.63; P = 8.22 × 10-6). Polygenic risk scores for SCZ were positively associated with clozapine vs other antipsychotic use (OR, 1.41; 95% CI, 1.22-1.63; P = 2.98 × 10-6), suggesting a higher likelihood of clozapine prescriptions among individuals with higher PRS-SCZ. Conclusions and Relevance: In this study, PRS-SCZ loading differed between groups of individuals with SSD, their relatives, and unrelated healthy controls, with patients taking clozapine at the far end of PRS-SCZ loading. Additionally, PRS-SCZ was associated with a higher likelihood of clozapine prescribing. Our findings may inform early intervention and prognostic studies of the value of using PRS-SCZ to personalize antipsychotic treatment.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu