Polygenic liability for antipsychotic dosage and polypharmacy - a real-world registry and biobank study

Elise Koch*, Anders Kämpe, Maris Alver, Sindri Sigurðarson, Guðmundur Einarsson, Juulia Partanen, Robert L. Smith, Piotr Jaholkowski, Heidi Taipale, Markku Lähteenvuo, Nils Eiel Steen, Olav B. Smeland, Srdjan Djurovic, Espen Molden, Engilbert Sigurðsson, Hreinn Stefánsson, Kári Stefánsson, Aarno Palotie, Lili Milani, Kevin S. O’ConnellOle A. Andreassen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Genomic prediction of antipsychotic dose and polypharmacy has been difficult, mainly due to limited access to large cohorts with genetic and drug prescription data. In this proof of principle study, we investigated if genetic liability for schizophrenia is associated with high dose requirements of antipsychotics and antipsychotic polypharmacy, using real-world registry and biobank data from five independent Nordic cohorts of a total of N = 21,572 individuals with psychotic disorders (schizophrenia, bipolar disorder, and other psychosis). Within regression models, a polygenic risk score (PRS) for schizophrenia was studied in relation to standardized antipsychotic dose as well as antipsychotic polypharmacy, defined based on longitudinal prescription registry data as well as health records and self-reported data. Meta-analyses across the five cohorts showed that PRS for schizophrenia was significantly positively associated with prescribed (standardized) antipsychotic dose (beta(SE) = 0.0435(0.009), p = 0.0006) and antipsychotic polypharmacy defined as taking ≥2 antipsychotics (OR = 1.10, CI = 1.05–1.21, p = 0.0073). The direction of effect was similar in all five independent cohorts. These findings indicate that genotypes may aid clinically relevant decisions on individual patients´ antipsychotic treatment. Further, the findings illustrate how real-world data have the potential to generate results needed for future precision medicine approaches in psychiatry.

Original languageEnglish
Pages (from-to)1113-1119
Number of pages7
JournalNeuropsychopharmacology
Volume49
Issue number7
Early online date6 Jan 2024
DOIs
Publication statusPublished - Jun 2024

Bibliographical note

© 2024. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.

Other keywords

  • Humans
  • Middle Aged
  • Male
  • Multifactorial Inheritance
  • Polypharmacy
  • Biological Specimen Banks
  • Psychotic Disorders/drug therapy
  • Registries
  • Female
  • Adult
  • Antipsychotic Agents/administration & dosage
  • Schizophrenia/drug therapy
  • Aged
  • Cohort Studies

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