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Genetic risk of clozapine-induced leukopenia and neutropenia: a genome-wide association study
- Source :
- Translational Psychiatry, Translational Psychiatry, Vol 11, Iss 1, Pp 1-10 (2021)
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group UK, 2021.
-
Abstract
- 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 CIN cases, and 1,654 controls) of Chinese descent were included. Data from common and rare single nucleotide polymorphisms (SNPs) were tested for association. The authors also performed a trans-ancestry meta-analysis with GWAS results of European individuals from the Clozapine-Induced Agranulocytosis Consortium (CIAC). Results The authors identified several novel loci reaching the threshold of genome-wide significance level (P −8). Three novel loci were associated with CIL while six were associated with CIN, and two T cell related genes (TRAC and TRAT1) were implicated. The authors also observed that one locus with evidence close to genome-wide significance (P = 5.08 × 10−8) was near the HLA-B gene in the major histocompatibility complex region in the trans-ancestry meta-analysis. Conclusions The associations provide novel and valuable understanding of the genetic and immune causes of CIL and CIN, which is useful for improving clinical management of clozapine related treatment for schizophrenia. Causal variants and related underlying molecular mechanisms need to be understood in future developments.
- Subjects :
- 0301 basic medicine
Neutropenia
Locus (genetics)
Genome-wide association study
Single-nucleotide polymorphism
Neurosciences. Biological psychiatry. Neuropsychiatry
Bioinformatics
Article
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Humans
Medicine
Clozapine
Biological Psychiatry
Leukopenia
business.industry
Medical genetics
Correction
medicine.disease
Psychiatry and Mental health
030104 developmental biology
Schizophrenia
Genetic marker
medicine.symptom
business
030217 neurology & neurosurgery
Antipsychotic Agents
Genome-Wide Association Study
medicine.drug
RC321-571
Subjects
Details
- Language :
- English
- ISSN :
- 21583188
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Translational Psychiatry
- Accession number :
- edsair.doi.dedup.....7fb3f16ce1ddf9865fee7c4c38052d6a