Genetic risk of clozapine-induced leukopenia and neutropenia: a genome-wide association study

  title={Genetic risk of clozapine-induced leukopenia and neutropenia: a genome-wide association study},
  author={Jianhua Chen and Ping Yang and Qian Zhang and Ruirui Chen and Pengkun Wang and Benxiu Liu and Wensheng Sun and Xuemin Jian and Si-Ying Xiang and Juan Zhou and Ningning Li and Ke Wang and Chengwen Gao and Ya Wen and Chuanhong Wu and Jinmai Zhang and Yalin Zhao and Qiangzhen Yang and Meihang Li and Robert J. Stewart and Yuanchao Sun and Dun Pan and Y Niu and Zhuo Wang and Yifeng Xu and Xing-wang Li and Lin He and Zhiqiang Li and Yongyong Shi},
  journal={Translational Psychiatry},
Background Clozapine is considered to be the most effective antipsychotic medication for schizophrenia. However, it is associated with several adverse effects such as leukopenia, and the underlying mechanism has not yet been fully elucidated. The authors performed a genome-wide association study (GWAS) in a Chinese population to identify genetic markers for clozapine-induced leukopenia (CIL) and clozapine-induced neutropenia (CIN). Methods A total of 1879 patients (225 CIL cases, including 43… 

Two Patients with Schizophrenia Treated with Clozapine Developed Neutropenia After Receiving a COVID-19 Vaccine

Physicians need to have a strict follow-up protocol in place for patients after vaccination for COVID-19, as two cases of patients with schizophrenia who were treated with clozapine and showed neutropenia after receiving a CO VID-19 vaccine were observed.



Genome-wide common and rare variant analysis provides novel insights into clozapine-associated neutropenia

The results implicate biological pathways through which clozapine may act to cause this serious adverse effect of schizophrenia, and identify gene-wide associations of uncommon non-synonymous variants within UBAP2 and STARD9.

Genetics of clozapine-associated neutropenia: recent advances, challenges and future perspective

An overview of the current understanding of the genetics of clozapine-associated agranulocytosis and neutropenia is provided and recent findings relating to the Duffy-null genotype and its association with benign neutropania in individuals with African ancestry are described.

Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles

Two loci in the major histocompatibility complex are independently associated with clozapine-induced agranulocytosis/granulocytopenia (CIAG), and these associations dovetail with the roles of these genes in immunogenetic phenotypes and adverse drug responses for other medications, and provide insight into the pathophysiology of CIAG.

More than 25 years of genetic studies of clozapine-induced agranulocytosis

It is concluded that CIA is most likely a complex, polygenic trait, which may hamper efforts to the development of a genetic predictor test with clinical relevance, and it is necessary to apply more rigorous standards of phenotyping and study much larger sample sizes.

A genome-wide association study in individuals of African ancestry reveals the importance of the Duffy-null genotype in the assessment of clozapine-related neutropenia

The results indicate the relevance of the rs2814778 genotype for those taking clozapine and its potential as a pharmacogenetic test, dependent on the outcome of additional safety studies, to assist decision making in the initiation and on-going management of clozAPine treatment.

Mechanism of Clozapine-Induced Agranulocytosis

Evidence exists to implicate both the major histocompatibility complex antigens and heat shock protein variants in determining individual susceptibility, although more patients of different ethnic backgrounds need to be studied.

Use of Clozapine for the Treatment of Schizophrenia: Findings of the 2006 Research on the China Psychotropic Prescription Studies

  • T. SiYun-shu Zhang Xin Yu
  • Psychology, Medicine
    Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology
  • 2012
Age, sex, professional help-seeking behaviors, duration of illness, economic status, educational level, and clinical manifestations were associated with the use of clozapine in China in 2006; however, use of the antipsychotic varies among provinces, and demographic and clinical factors play important roles in the prescription.

HLA-B38 and clozapine-induced agranulocytosis in Israeli Jewish schizophrenic patients.

  • A. ValevskiT. Klein Abraham Weizman
  • Medicine, Psychology
    European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics
  • 1998
HLA typing was performed in 61 Jewish Israeli schizophrenic patients to suggest that major histocompatibility complex gene products could be involved in clozapine-mediated haematological complications.