title: Polygenic Risk Score for Schizophrenia and Treatment-Resistant Schizophrenia.
abstract: Treatment-resistant schizophrenia (TRS) affects around one-third of individuals with schizophrenia. Although a number of sociodemographic and clinical predictors of TRS have been identified, data on the genetic risk of TRS are sparse. We aimed to investigate the association between a polygenic risk score for schizophrenia and treatment resistance in patients with schizophrenia. We conducted a nationwide, population-based follow-up study among all Danish individuals born after 1981 and with an incident diagnosis of schizophrenia between 1999 and 2007. Based on genome-wide data polygenic risk scores for schizophrenia were calculated in 862 individuals with schizophrenia. TRS was defined as either clozapine initiation or at least 2 periods of different antipsychotic monotherapies and still being hospitalized. We estimated hazard rate ratios (HRs) for TRS in relation to the polygenic risk score while adjusting for population stratification, age, sex, geographical area at birth, clinical treatment setting, psychiatric comorbidity, and calendar year. Among the 862 individuals with schizophrenia, 181 (21.0%) met criteria for TRS during 4674 person-years of follow-up. We found no significant association between the polygenic risk score and TRS, adjusted HR = 1.13 (95% CI: 0.95-1.35). Based on these results, the use of the polygenic risk score for schizophrenia to identify individuals with TRS is at present inadequate to be of clinical utility at the individual patient level. Future research should include larger genetic samples in combination with non-genetic markers. Moreover, a TRS-specific developed polygenic risk score would be of great interest towards early prediction of TRS.
authors.affiliation: National Centre for Register-based Research, Aarhus BSS, Aarhus University, Aarhus, Denmark.|iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.|Centre for Integrated Register-based Research, CIRRAU, Aarhus University, Aarhus, Denmark.
authors.forename: Theresa
authors.initials: T
authors.lastname: Wimberley
authors.affiliation: National Centre for Register-based Research, Aarhus BSS, Aarhus University, Aarhus, Denmark.|iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.|Centre for Integrated Register-based Research, CIRRAU, Aarhus University, Aarhus, Denmark.
authors.forename: Christiane
authors.initials: C
authors.lastname: Gasse
authors.affiliation: National Centre for Register-based Research, Aarhus BSS, Aarhus University, Aarhus, Denmark.|iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.|Child and Adolescent Mental Health Centre-Mental Health Services Capital Region, Copenhagen, Denmark.|Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.
authors.forename: Sandra Melanie
authors.initials: SM
authors.lastname: Meier
authors.affiliation: National Centre for Register-based Research, Aarhus BSS, Aarhus University, Aarhus, Denmark.|iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.|Centre for Integrated Register-based Research, CIRRAU, Aarhus University, Aarhus, Denmark.
authors.forename: Esben
authors.initials: E
authors.lastname: Agerbo
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: James H
authors.initials: JH
authors.lastname: MacCabe
authors.affiliation: National Centre for Register-based Research, Aarhus BSS, Aarhus University, Aarhus, Denmark.|iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.|Centre for Integrated Register-based Research, CIRRAU, Aarhus University, Aarhus, Denmark.
authors.forename: Henriette Thisted
authors.initials: HT
authors.lastname: Horsdal
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003718:Denmark; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D020412:Multifactorial Inheritance / Q000235:genetics*; D012042:Registries / Q000706:statistics & numerical data*; D012306:Risk; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents
keywords: antipsychotics; clozapine; genetic liability; treatment resistance