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

The Pharmacogenomics Journal volume 17, pages 304–311 (2017)Cite this article

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Abstract

Clozapine is one of the most effective atypical antipsychotic drugs prescribed to patients with treatment-resistant schizophrenia. Approximately 1% of patients experience potential life-threatening adverse effects in the form of agranulocytosis, greatly hindering its applicability in clinical practice. The etiology of clozapine-induced agranulocytosis (CIA) remains unclear, but is thought to be a heritable trait. We reviewed the genetic studies of CIA published thus far. One recurrent finding from early candidate gene study to more recent genome-wide analysis is that of the involvement of human leukocyte antigen locus. We conclude that CIA is most likely a complex, polygenic trait, which may hamper efforts to the development of a genetic predictor test with clinical relevance. To decipher the genetic architecture of CIA, it is necessary to apply more rigorous standards of phenotyping and study much larger sample sizes.

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Authors and Affiliations

  1. Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands

    S A J de With, R S Kahn & R A Ophoff

  2. Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands

    S L Pulit

  3. Department of Cognitive Neuroscience, Radboud University Nijmegen Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands

    W G Staal

  4. Department of Psychiatry, Radboud University Nijmegen Medical Center and Karakter, Center for Child and Adolescent Psychiatry, Nijmegen, The Netherlands

    W G Staal

  5. UCLA Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA

    R A Ophoff

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de With, S., Pulit, S., Staal, W. et al. More than 25 years of genetic studies of clozapine-induced agranulocytosis. Pharmacogenomics J 17, 304–311 (2017). https://doi.org/10.1038/tpj.2017.6

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