ArticleBiological psychiatry2016
Pharmacogenomic Study of Clozapine-Induced Agranulocytosis/Granulocytopenia in a Japanese Population.
Article in Biological psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 73 citations in OpenAlex.
- Pharmacogenomics of Clozapine-induced agranulocytosis: a systematic review and meta-analysis.The pharmacogenomics journal · 2022Pooled it
- Genetic risk of clozapine-induced leukopenia and neutropenia: a genome-wide association study.Translational psychiatry · 2021Pooled it
- Association between initial 30-day cumulative clozapine dose and risk of agranulocytosis: A nationwide register-based cohort study.Psychiatry and clinical neurosciences · 2026Article
- The evolving landscape of pharmacogenomics: Current achievements and future directions.Pharmacological reviews · 2026Review
- Mental health nurses' knowledge and attitudes toward clozapine management protocols challenges and implications for clinical practice: A narrative review.AIMS public health · 2026Review
- Clozapine Induces Agranulocytosis via Inflammatory and Hematopoietic Cytokine Induction of the JAK-STAT Signaling Pathway: Evidence From Network Pharmacology and Molecular Docking.CNS neuroscience & therapeutics · 2025Article
- Mining Real-World Big Data to Characterize Adverse Drug Reaction Quantitatively: Mixed Methods Study.Journal of medical Internet research · 2024Article
- Clinical Utility and Implementation of Pharmacogenomics for the Personalisation of Antipsychotic Treatments.Pharmaceutics · 2024Review
- Dopaminergic dysfunction and excitatory/inhibitory imbalance in treatment-resistant schizophrenia and novel neuromodulatory treatment.Molecular psychiatry · 2022Review
- Distinctive pattern of neutrophil count change in clozapine-associated, life-threatening agranulocytosis.Schizophrenia (Heidelberg, Germany) · 2022Article
- Integrative omics of schizophrenia: from genetic determinants to clinical classification and risk prediction.Molecular psychiatry · 2022Review
- Trends in big data analyses by multicenter collaborative translational research in psychiatry.Psychiatry and clinical neurosciences · 2022Review
- HLA-associated adverse drug reactions - scoping review.Clinical and translational science · 2021Article
- Cost effectiveness of pharmacogenetic-guided clozapine administration based on risk of HLA variants in Japan and the UK.Translational psychiatry · 2021Article
- Genetic Testing for Antipsychotic Pharmacotherapy: Bench to Bedside.Behavioral sciences (Basel, Switzerland) · 2021Review
- Progress in study on the association between HLA genetic variation and adverse drug reactions.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2021Article
- Clozapine Is Better Tolerated in Younger Patients: Risk Factors for Discontinuation from a Nationwide Database in Japan.Psychiatry investigation · 2021Article
- Genome-Wide Association Study of Metamizole-Induced Agranulocytosis in European Populations.Genes · 2020Article
- Omics era in forensic medicine: towards a new ageTurkish journal of medical sciences · 2020Review
- Potential pharmacogenomic targets in bipolar disorder: considerations for current testing and the development of decision support tools to individualize treatment selection.International journal of bipolar disorders · 2020Review
Corrections and comments
- Commented on by
Authors and funding
37 authors at 18 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundClozapine-induced agranulocytosis (CIA)/clozapine-induced granulocytopenia (CIG) (CIAG) is a life-threatening event for schizophrenic subjects treated with clozapine.
methodsTo examine the genetic factor for CIAG, a genome-wide pharmacogenomic analysis was conducted using 50 subjects with CIAG and 2905 control subjects.
resultsWe identified a significant association in the human leukocyte antigen (HLA) region (rs1800625, p = 3.46 × 10(-9), odds ratio [OR] = 3.8); therefore, subsequent HLA typing was performed. We detected a significant association of HLA-B*59:01 with CIAG (p = 3.81 × 10(-8), OR = 10.7) and confirmed this association by comparing with an independent clozapine-tolerant control group (n = 380, p = 2.97 × 10(-5), OR = 6.3). As we observed that the OR of CIA (OR: 9.3~15.8) was approximately double that in CIG (OR: 4.4~7.4), we hypothesized that the CIG subjects were a mixed population of those who potentially would develop CIA and those who would not develop CIA (non-CIA). This hypothesis allowed the proportion of the CIG who were non-CIA to be calculated, enabling us to estimate the positive predictive value of the nonrisk allele on non-CIA in CIG subjects. Assuming this model, we estimated that 1) ~50% of CIG subjects would be non-CIA; and 2) ~60% of the CIG subjects without the risk allele would be non-CIA and therefore not expected to develop CIA.
conclusionsOur results suggest that HLA-B*59:01 is a risk factor for CIAG in the Japanese population. Furthermore, if our model is true, the results suggest that rechallenging certain CIG subjects with clozapine may not be always contraindicated.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.