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

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 eff i cacy, and more than 50% change was considered as APD response. Associations between CNV burden, gene set, CNV loci and CNV break-point and APD eff i cacy 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 signi fi cant 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 eff i cacy ( 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 eff i cacy and synaptic pathway involved in neurotransmitter was highlighted.