Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Genomic stratification of clozapine prescription patterns using schizophrenia polygenic scores

Kappel, Djenifer B., Legge, Sophie E., Hubbard, Leon, Willcocks, Isabella R. ORCID:, O'Connell, Kevin S., Smith, Robert L., Molden, Espen, Andreassen, Ole A., King, Adrian, Jansen, John, Helthuis, Marinka, Owen, Michael J. ORCID:, O'Donovan, Michael C. ORCID:, Walters, James T. R. ORCID: and Pardinas, Antonio F. ORCID: 2023. Genomic stratification of clozapine prescription patterns using schizophrenia polygenic scores. Biological Psychiatry 93 , pp. 149-156. 10.1016/j.biopsych.2022.07.014

[thumbnail of Ar PIIS0006322322014494.pdf]
PDF - Published Version
Available under License Creative Commons Attribution.

Download (413kB) | Preview
License URL:
License Start date: 5 August 2022


Background Treatment-resistant schizophrenia affects approximately 30% of individuals with the disorder. Clozapine is the medication of choice in treatment-resistant schizophrenia, but optimizing administration and dose titration is complex. The identification of factors influencing clozapine prescription and response, including genetics, is of interest in a precision psychiatry framework. Methods We used linear regression models accounting for demographic, pharmacological, and clinical covariates to determine whether a polygenic risk score (PRS) for schizophrenia would be associated with the highest dose recorded during clozapine treatment. Analyses were performed across 2 independent multiancestry samples of individuals from a UK patient monitoring system, CLOZUK2 (n = 3133) and CLOZUK3 (n = 909), and a European sample from a Norwegian therapeutic drug monitoring service (n = 417). In a secondary analysis merging both UK cohorts, logistic regression models were used to estimate the relationship between schizophrenia PRSs and clozapine doses classified as low, standard, or high. Results After controlling for relevant covariates, the schizophrenia PRS was correlated with the highest clozapine dose on record for each individual across all samples: CLOZUK2 (β = 12.22, SE = 3.78, p = .001), CLOZUK3 (β = 12.73, SE = 5.99, p = .034), and the Norwegian cohort (β = 46.45, SE = 18.83, p = .014). In a secondary analysis, the schizophrenia PRS was associated with taking clozapine doses >600 mg/day (odds ratio = 1.279, p = .006). Conclusions The schizophrenia PRS was associated with the highest clozapine dose prescribed for an individual in records from 3 independent samples, suggesting that the genetic liability for schizophrenia might index factors associated with therapeutic decisions in cohorts of patients with treatment-resistant schizophrenia.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Advanced Research Computing @ Cardiff (ARCCA)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Elsevier
ISSN: 0006-3223
Funders: MRC
Date of First Compliant Deposit: 25 July 2022
Date of Acceptance: 19 July 2022
Last Modified: 16 Jul 2024 10:05

Citation Data

Cited 1 time in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item


Downloads per month over past year

View more statistics