Pharmacokinetics and pharmacogenomics of clozapine in an ancestrally diverse sample: a longitudinal analysis and genome-wide association study using UK clinical monitoring data.
Pardiñas AF, Kappel DB, Roberts M et al.
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Abstract
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The antipsychotic, clozapine, is the only licensed drug against the treatment-resistant symptoms that affect 20-30% of people with schizophrenia. Clozapine is markedly underprescribed, partly because of concerns about its narrow therapeutic range and adverse drug reaction profile. Both concerns are linked to drug metabolism, which varies across populations globally and is partly genetically determined. Our study aimed to use a cross-ancestry genome-wide association study (GWAS) design to investigate variations in clozapine metabolism within and between genetically inferred ancestral backgrounds, to discover genomic associations to clozapine plasma concentrations, and to assess the effects of pharmacogenomic predictors across different ancestries.
3,677 European ancestry individuals, 243 Sub-Saharan African ancestry individuals, 122 Greater Middle Eastern (Middle Eastern, North African or Persian) individuals, 244 South Asian ancestry individuals, 41 East Asian ancestry individuals, 168 NR ancestry, Other admixed ancestry individuals
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