Contribution of copy number variants on antipsychotic treatment response in Han Chinese patients with schizophrenia.
EBioMedicine
; 105: 105195, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38870545
ABSTRACT
BACKGROUND:
Response to antipsychotic drugs (APD) varies greatly among individuals and is affected by genetic factors. This study aims to demonstrate genome-wide associations between copy number variants (CNVs) and response to APD in patients with schizophrenia.METHODS:
A total of 3030 patients of Han Chinese ethnicity randomly received APD (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, haloperidol and perphenazine) treatment for six weeks. This study is a secondary data analysis. Percentage change on the Positive and Negative Syndrome Scale (PANSS) reduction was used to assess APD efficacy, and more than 50% change was considered as APD response. Associations between CNV burden, gene set, CNV loci and CNV break-point and APD efficacy were analysed.FINDINGS:
Higher CNV losses burden decreased the odds of 6-week APD response (OR = 0.66 [0.44, 0.98]). CNV losses in synaptic pathway involved in neurotransmitters were associated with 2-week PANSS reduction rate. CNV involved in sialylation (1p31.1 losses) and cellular metabolism (19q13.32 gains) associated with 6-week PANSS reduction rate at genome-wide significant level. Additional 36 CNVs associated with PANSS factors improvement. The OR of protective CNVs for 6-week APD response was 3.10 (95% CI 1.33-7.19) and risk CNVs was 8.47 (95% CI 1.92-37.43). CNV interacted with genetic risk score on APD efficacy (Beta = -1.53, SE = 0.66, P = 0.021). The area under curve to differ 6-week APD response attained 80.45% (95% CI 78.07%-82.82%).INTERPRETATION:
Copy number variants contributed to poor APD efficacy and synaptic pathway involved in neurotransmitter was highlighted.FUNDING:
National Natural Science Foundation of China, National Key R&D Program of China, China Postdoctoral Science Foundation.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esquizofrenia
/
Antipsicóticos
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Estudo de Associação Genômica Ampla
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Variações do Número de Cópias de DNA
Limite:
Adult
/
Female
/
Humans
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Male
/
Middle aged
País/Região como assunto:
Asia
Idioma:
En
Revista:
EBioMedicine
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Holanda