{"doi":"10.1016/j.biopsych.2022.07.014","title":"Genomic Stratification of Clozapine Prescription Patterns Using Schizophrenia Polygenic Scores","abstract":"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.","journal":"Biological Psychiatry","year":2022,"id":250052,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8733,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":28801,"name":"Sophie E. Legge","orcid":"0000-0001-6617-0289","position":1,"is_corresponding":false},{"id":252392,"name":"Leon Hubbard","orcid":"0000-0002-0064-6755","position":2,"is_corresponding":false},{"id":891470,"name":"Isabella Willcocks","orcid":"0000-0002-3568-5236","position":3,"is_corresponding":false},{"id":256438,"name":"Kevin S. O’Connell","orcid":"0000-0002-6865-8795","position":4,"is_corresponding":false},{"id":326994,"name":"Robert L. Smith","orcid":"0000-0001-6789-7076","position":5,"is_corresponding":false},{"id":326997,"name":"Espen Molden","orcid":"0000-0001-6190-2751","position":6,"is_corresponding":false},{"id":52934,"name":"Ole A. Andreassen","orcid":"0000-0002-4461-3568","position":7,"is_corresponding":false},{"id":892219,"name":"Adrian King","orcid":null,"position":8,"is_corresponding":false},{"id":441443,"name":"John A. Jansen","orcid":"0000-0003-3077-8617","position":9,"is_corresponding":false},{"id":892220,"name":"Marinka Helthuis","orcid":null,"position":10,"is_corresponding":false},{"id":1100,"name":"Michael J. Owen","orcid":"0000-0003-4798-0862","position":11,"is_corresponding":false},{"id":1159,"name":"Michael C O'Donovan","orcid":"0000-0001-7073-2379","position":12,"is_corresponding":false},{"id":263899,"name":"James Walters","orcid":"0000-0002-6980-4053","position":13,"is_corresponding":false},{"id":263898,"name":"Antonio F. Pardiñas","orcid":"0000-0001-6845-7590","position":14,"is_corresponding":false},{"id":891469,"name":"Djenifer B. Kappel","orcid":"0000-0002-2906-5911","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T00:24:28.242323Z","pmid":"36244804","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}