Update on next generation sequencing of pharmacokinetics-related genes: Development of the PKseq panel, a platform for amplicon sequencing of drug-metabolizing enzyme and drug transporter genes

Fukunaga, Koya; Momozawa, Yukihide; Mushiroda, Taisei

doi:10.1016/j.dmpk.2020.11.005

Cited by 3 publications

(1 citation statement)

References 38 publications

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“…More importantly, a large number of rare variants with large effects were missed by current GWAS [13,14]. Whole-exome sequencing (WES) offers a cost-effective strategy for investigating rare variants in drug-response studies [15]. Wang et al conducted a pharmacogenomic WES study which found a greater burden of rare damaging variants in the reduced NMDA(N-methyl-D-aspartate)-mediated synaptic currents and reduced AMPA (α-amino-3-hydroxy-5-methy-4-isoxazole propionic acid)-mediated synaptic current gene sets curated in patients with poor response to antipsychotic medications, but no SNPs and single gene achieved genome-wide significance [16].…”

Section: Introductionmentioning

confidence: 99%

Different responses to risperidone treatment in Schizophrenia: a multicenter genome-wide association and whole exome sequencing joint study

Zhao

et al. 2022

Transl Psychiatry

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Risperidone is routinely used in the clinical management of schizophrenia, but the treatment response is highly variable among different patients. The genetic underpinnings of the treatment response are not well understood. We performed a pharmacogenomic study of the treatment response to risperidone in patients with schizophrenia by using a SNP microarray -based genome-wide association study (GWAS) and whole exome sequencing (WES)-based GWAS. DNA samples were collected from 189 patients for the GWAS and from 222 patients for the WES after quality control in multiple centers of China. Antipsychotic response phenotypes of patients who received eight weeks of risperidone treatment were quantified with percentage change on the Positive and Negative Syndrome Scale (PANSS). The GWAS revealed a significant association between several SNPs and treatment response, such as three GRM7 SNPs (rs141134664, rs57521140, and rs73809055). Gene-based analysis in WES revealed 13 genes that were associated with antipsychotic response, such as GPR12 and MAP2K3. We did not identify shared loci or genes between GWAS and WES, but association signals tended to cluster into the GPCR gene family and GPCR signaling pathway, which may play an important role in the treatment response etiology. This study may provide a research paradigm for pharmacogenomic research, and these data provide a promising illustration of our potential to identify genetic variants underlying antipsychotic responses and may ultimately facilitate precision medicine in schizophrenia.

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