Exome sequence analysis of Finnish patients with clozapine-induced agranulocytosis

Tiwari, Arun; Need, Anna C.; Lohoff, Falk W.; Zai, Clement C.; Chowdhury, Nabilah I.; Müller, Daniel J.; Putkonen, Anu; Repo-Tiihonen, Eila; Hallikainen, Tero; Yağcıoğlu, A. Elif Anıl; Tiihonen, Jari; Kennedy, James L.; Meltzer, Herbert Y.

doi:10.1038/mp.2013.74

Cited by 21 publications

(13 citation statements)

References 11 publications

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“…PGx explorations based on NGS/WES identified several novel variants potentially able to modify the therapeutic efficacy of drugs, e.g., clopidogrel [292], escitalopram [293], clozapine [294] and paclitaxel [295]. NGS can reveal both known and rare PGx variants in one test and is therefore a suitable method for the identification of novel relevant variants related to the use of certain drugs.…”

Section: Pharmacogeneticsmentioning

confidence: 99%

Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification

Kamps

Brandão

Bosch

et al. 2017

IJMS

387

294

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Next-generation sequencing (NGS) technology has expanded in the last decades with significant improvements in the reliability, sequencing chemistry, pipeline analyses, data interpretation and costs. Such advances make the use of NGS feasible in clinical practice today. This review describes the recent technological developments in NGS applied to the field of oncology. A number of clinical applications are reviewed, i.e., mutation detection in inherited cancer syndromes based on DNA-sequencing, detection of spliceogenic variants based on RNA-sequencing, DNA-sequencing to identify risk modifiers and application for pre-implantation genetic diagnosis, cancer somatic mutation analysis, pharmacogenetics and liquid biopsy. Conclusive remarks, clinical limitations, implications and ethical considerations that relate to the different applications are provided.

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Section: Pharmacogeneticsmentioning

confidence: 99%

Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification

Kamps

Brandão

Bosch

et al. 2017

IJMS

387

294

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“…3, 4, 5, 6, 7, 8 A small exome sequencing study of CIAG was unrevealing 9 . While nominally significant HLA associations have been reported, no study to our knowledge has reported unequivocal statistical significance or the dissection of the complex linkage disequilibrium (LD) relationships in the MHC.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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Clozapine is a particularly effective antipsychotic medication but its use is curtailed by the risk of clozapine-induced agranulocytosis/granulocytopenia (CIAG), a severe adverse drug reaction occurring in up to 1% of treated individuals. Identifying genetic risk factors for CIAG could enable safer and more widespread use of clozapine. Here we perform the largest and most comprehensive genetic study of CIAG to date by interrogating 163 cases using genome-wide genotyping and whole-exome sequencing. We find that two loci in the major histocompatibility complex are independently associated with CIAG: a single amino acid in HLA-DQB1 (126Q) (P=4.7×10−14, odds ratio, OR=0.19, 95% CI 0.12–0.29) and an amino acid change in the extracellular binding pocket of HLA-B (158T) (P=6.4×10−10, OR=3.3, 95% CI 2.3–4.9). 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.

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“…Whole exome sequencing done in a Finnish study [76] focused on three genes nominally associated with clozapine agranulocytosis: PPFIA4 (protein tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting protein (liprin),a4), ubiquitin-specific peptidase 4 (USP43) and actinin -a-1 (ACTN1). PPFIA4 belongs to liprin, a protein family that interacts with leukocyte common antigen-related receptor protein tyrosine phosphatase F and plays a role in maintaining cell-cell adhesion [77]. The SNP of the PPFIA4 rs903365 is recognized as a potential weak promoter/ enhancer region.…”

Section: Ethnic Differences Hla Subtypes In Clozapine Induced Agranulmentioning

confidence: 99%

Psychotropic Idiosyncratic Drug Reactions: A Brief Review of Proposed Mechanisms

Tanu¹,

Andrés²,

Luba³

et al. 2019

Int J Psychiatr Res

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Exome sequence analysis of Finnish patients with clozapine-induced agranulocytosis

Cited by 21 publications

References 11 publications

Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification

Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification

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

Psychotropic Idiosyncratic Drug Reactions: A Brief Review of Proposed Mechanisms

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