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

S. A.J. de With, S. L. Pulit, W. G. Staal, R. S. Kahn, R. A. Ophoff

Research output: Contribution to journalReview articlepeer-review

32 Scopus citations

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.

Original languageEnglish
Pages (from-to)304-311
Number of pages8
JournalPharmacogenomics Journal
Volume17
Issue number4
DOIs
StatePublished - 1 Jul 2017
Externally publishedYes

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