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Lin, B D, Pinzón-Espinosa, J, Blouzard, E, Van Der Horst, M Z, Okhuijsen-pfeifer, C, Van Eijk, K R, Guloksuz, S, Peyrot, W J, Luykx, J J, Hasan, A, Wagner, E, Pantelis, C, Everall, I P, Ayhan, Y, Babaoğlu, M O, Bak, M, Alink, W, Beld, E, Bouhuis, A, Edlinger, M, Erdoğan, I M, Gutwinski, S, Hallikainen, T, Jeger-land, E, Lähteenvuo, M, De Koning, M B, Morgenroth, C, Müderrisoğlu, A, Oviedo-salcedo, T, Schreiter, S, Repo-tiihonen, E, Tuppurainen, H, Veereschild, M, Veerman, S R T, Cohen, D, de Vos, M, Bogers, J P A M, Anıl Yağcıoğlu, A E, Tiihonen, J, .... |
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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, ... |