PDF(Pubmed)
Abstract：
Computational methods analyze genomic data to identify genetic variants linked to drug responses, thereby guiding personalized medicine. This study analyzed 942 whole-genome sequences from the Electricity Generating Authority of Thailand (EGAT) cohort to establish a population-specific pharmacogenomic database (TPGxD-1) in the Thai population. Sentieon (version 201808.08) implemented the GATK best workflow practice for variant calling. We then annotated variant call format (VCF) files using Golden Helix VarSeq 2.5.0 and employed Stargazer v2.0.2 for star allele analysis. The analysis of 63 very important pharmacogenes (VIPGx) reveals 85,566 variants, including 13,532 novel discoveries. Notably, we identified 464 known PGx variants and 275 clinically relevant novel variants. The phenotypic prediction of 15 VIPGx demonstrated a varied metabolic profile for the Thai population. Genes like CYP2C9 (9%), CYP3A5 (45.2%), CYP2B6 (9.4%), NUDT15 (15%), CYP2D6 (47%) and CYP2C19 (43%) showed a high number of intermediate metabolizers; CYP3A5 (41%), and CYP2C19 (9.9%) showed more poor metabolizers. CYP1A2 (52.7%) and CYP2B6 (7.6%) were found to have a higher number of ultra-metabolizers. The functional prediction of the remaining 10 VIPGx genes reveals a high frequency of decreased functional alleles in SULT1A1 (12%), NAT2 (84%), and G6PD (12%). SLCO1B1 reports 20% poor functional alleles, while PTGIS (42%), SLCO1B1 (4%), and TPMT (5.96%) showed increased functional alleles. This study discovered new variants and alleles in the 63 VIPGx genes among the Thai population, offering insights into advancing clinical pharmacogenomics (PGx). However, further validation is needed using other computational and genotyping methods.
摘要：
计算方法分析基因组数据，以确定与药物反应相关的遗传变异，从而指导个性化医疗。这项研究分析了来自泰国发电局（EGAT）队列的942个全基因组序列，以在泰国人群中建立特定于人群的药物基因组数据库（TPGxD-1）。Sentieon（版本201808.08）实施了GATK变体调用的最佳工作流程实践。然后，我们使用GoldenHelixVarSeq2.5.0注释变体调用格式（VCF）文件，并使用Stargazerv2.0.2进行星形等位基因分析。对63种非常重要的药物基因（VIPGx）的分析揭示了85,566种变体，包括13532个新发现。值得注意的是,我们鉴定出464个已知PGx变异体和275个临床相关的新变异体.15个VIPGx的表型预测表明，泰国人群的代谢谱各不相同。基因如CYP2C9（9％），CYP3A5（45.2%），CYP2B6（9.4%），NUDT15（15%），CYP2D6（47％）和CYP2C19（43％）显示出大量的中间代谢者；CYP3A5（41％），和CYP2C19（9.9％）显示更多的代谢不良。发现CYP1A2（52.7％）和CYP2B6（7.6％）具有较高数量的超代谢因子。其余10个VIPGx基因的功能预测显示，SULT1A1中功能等位基因减少的频率很高（12％），NAT2（84%），和G6PD（12%）。SLCO1B1报告了20%的不良功能等位基因，而PTGIS（42%），SLCO1B1（4%），和TPMT(5.96%)显示增加的功能等位基因。这项研究在泰国人群中的63个VIPGx基因中发现了新的变异和等位基因，提供对推进临床药物基因组学(PGx)的见解。然而,需要使用其他计算和基因分型方法进一步验证.
