Dataset Information

Contribution of copy number variants on antipsychotic treatment response in Han Chinese patients with schizophrenia.

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.

SUBMITTER: Sun Y

PROVIDER: S-EPMC11225184 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature

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Publications

Contribution of copy number variants on antipsychotic treatment response in Han Chinese patients with schizophrenia.

Sun Yaoyao Y Zhang Yuyanan Y Lu Zhe Z Liao Yundan Y Feng Qidi Q Yu Mingrui M Chen Yu Y Kang Zhewei Z Feng Xiaoyang X Zhao Guorui G Sun Junyuan J Yang Yang Y Guo Liangkun L Zhang Dai D Bi Wenjian W Huang Hailiang H Yue Weihua W

EBioMedicine 20240614

<h4>Background</h4>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.<h4>Methods</h4>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 seconda ...[more]

PMID: 38870545

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Project description:BACKGROUND: Ghrelin (GHRL) is a pivotal peptide regulator of food intake, energy balance, and body mass. Weight gain (WG) is a common side effect of the atypical antipsychotics (AAPs) used to treat schizophrenia (SZ). Ghrelin polymorphisms have been associated with pathogenic variations in plasma lipid concentrations, blood pressure, plasma glucose, and body mass index (BMI). However, it is unclear whether GHRL polymorphisms are associated with WG due to AAPs. Furthermore, there is no evidence of an association between GHRL polymorphisms and SZ or the therapeutic response to AAPs. We explored these potential associations by genotyping GHRL alleles in SZ patients and controls. We also examined the relation between these SNPs and changes in metabolic indices during AAP treatment in SZ subgroups distinguished by high or low therapeutic response. METHODS: Four SNPs (Leu72Met, -501A/C, -604 G/A, and -1062 G > C) were genotyped in 634 schizophrenia patients and 606 control subjects. RESULTS: There were no significant differences in allele frequencies, genotype distributions, or the distributions of two SNP haplotypes between SZ patients and healthy controls (P > 0.05). There was also no significant difference in symptom reduction between genotypes after 8 weeks of AAP treatment as measured by positive and negative symptom scale scores (PANSS). However, the -604 G/A polymorphism was associated with a greater BMI increase in response to AAP administration in both APP responders and non-responders as distinguished by PANSS score reduction (P < 0.001). There were also significant differences in WG when the responder group was further subdivided according to the specific AAP prescribed (P < 0.05). CONCLUSIONS: These four GHRL gene SNPs were not associated with SZ in this Chinese Han population. The -604 G/A polymorphism was associated with significant BW and BMI increases during AAP treatment. Patients exhibiting higher WG showed greater improvements in positive and negative symptoms than patients exhibiting lower weight gain or weight loss.

Dataset Information

Contribution of copy number variants on antipsychotic treatment response in Han Chinese patients with schizophrenia.

Background

Methods

Findings

Interpretation

Funding

Publications

Contribution of copy number variants on antipsychotic treatment response in Han Chinese patients with schizophrenia.

Similar Datasets

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