在1000个基因组项目中使用全基因组序列的结构变异的药物遗传学分析
Carissa A Sherman1, Katrina G Claw1, Seung-Been Lee2
1Department of Biomedical Informatics, Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Scientific reports
|October 1, 2024
概括
这项研究使用全基因组测序对58个基因的全球药物遗传学 (PGx) 恒星等位基因和表型频率进行了分析. 它揭示了人群特异性变异,并确定了用于改进药物治疗的新型遗传变异.
科学领域:
- 基因组学就是基因组学.
- 药物遗传学 药物遗传学
- 人口遗传学 人口遗传学
背景情况:
- 药物遗传学 (PGx) 和基因药物相互作用越来越被理解,但人口水平的PGx变异需要进一步的表征.
- 了解全球PGx变异对于开发个性化药物和优化不同人群的药物疗效和安全至关重要.
研究的目的:
- 对58种药物基因的全球恒星等位基因和表型频率进行全面分析.
- 确定特定于种群的PGx变异,包括结构变异 (SV) 和小核酸变异 (SNV).
- 评估全基因组测序 (WGS) 在不同种群中的PGx基因型鉴定的实用性.
主要方法:
- 在1000个基因组项目 (N=2504;26个种群) 的高覆盖WGS数据上利用PyPGx,一个恒星基因组调用工具.
- 检测到的结构变体 (SV),如删除,重复和混合,以及SNV和插入删除变体.
- 与PyPGx衍生的恒星等位基和表型频率与药物基因组学知识库 (PharmGKB) 进行了比较.
主要成果:
- 在PyPGx调用和PharmGKB之间具有很高的一致性,具有显著的人口特异性的频率差异 (至少是两倍).
- 确认已知的SVs和发现的新型SVs尚未被定义为恒星等位基因.
- 确定了210个具有严重功能后果的SNV,目前尚未被定义为明星等位基因.
结论:
- 提供最新的,人口级恒星等位基和表型频率,包括SVs,作为一个有价值的资源.
- 突出显著的人群特异性PGx变异,需要量身定制的药物治疗.
- 展示了具有成本效益的WGS在全球多样化人口中进行全面的PGx基因型识别的潜力.
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