Contribution of copy number variants on antipsychotic treatment response in Han Chinese patients with schizophreniaResearch in context
Yaoyao Sun,
Yuyanan Zhang,
Zhe Lu,
Yundan Liao,
Qidi Feng,
Mingrui Yu,
Yu Chen,
Zhewei Kang,
Xiaoyang Feng,
Guorui Zhao,
Junyuan Sun,
Yang Yang,
Liangkun Guo,
Dai Zhang,
Wenjian Bi,
Hailiang Huang,
Weihua Yue
Affiliations
Yaoyao Sun
Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China
Yuyanan Zhang
Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China
Zhe Lu
Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China
Yundan Liao
Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China
Qidi Feng
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
Mingrui Yu
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
Yu Chen
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
Zhewei Kang
Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China
Xiaoyang Feng
Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China
Guorui Zhao
Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China
Junyuan Sun
Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China
Yang Yang
Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China
Liangkun Guo
Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China
Dai Zhang
Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China; PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China; Chinese Institute for Brain Research, Beijing 102206, China
Wenjian Bi
Department of Medical Genetics, School of Basic Medical Sciences, Peking University, Beijing 100191, China
Hailiang Huang
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Corresponding author. Massachusetts General Hospital Analytic and Translational Genetics Unit, Richard B. Simches Research Center, 185 Cambridge Street, CPZN 6802, Boston, MA 02114, USA.
Weihua Yue
Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China; PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China; Corresponding author. Institute of Mental Health, Peking University Sixth Hospital, No. 51 Hua Yuan Bei Road, Beijing 100191, China.
Summary: 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.
