化学疗法诱导的外围神经病变的药物基因组学使用电子健康记录衍生的定义:全基因组关联研究研究
Michael K Jones1, Andrew Nicklawsky2, Jonathan Shortt3,4
1Internal Medicine Residency, University of Colorado School of Medicine, Aurora, CO, United States. michael.k.jones@cuanschutz.edu.
概括
这项全基因组关联研究使用电子健康记录确定了与化疗诱导的外围神经病变 (CIPN) 相关的新基因. 这些发现可能会改善未来对CIPN发展的遗传研究.
科学领域:
- 药物基因组学 药物基因组学
- 遗传学 是一个遗传学.
- 在瘤学瘤学.
背景情况:
- 化疗诱导的周围神经病变 (CIPN) 是一种常见的剂量限制性毒性.
- 之前对CIPN的遗传研究受到小样本大小和数据提取挑战的限制.
- 电子健康记录 (EHR) 为药物基因组学研究中大规模数据收集提供了一个潜在的解决方案.
研究的目的:
- 进行全基因组关联研究 (GWAS),以确定与CIPN.相关的遗传变异.
- 利用基于EHR的CIPN定义来克服先前研究的局限性.
- 在大量患者队列中探索对CIPN的遗传倾向.
主要方法:
- 对具有生殖系遗传数据和化疗史的患者进行了GWAS.
- 使用EHR数据定义CIPN,包括神经病痛药物处方或神经病变诊断.
- 研究群体根据化疗类型 (白金,税,类) 分层进行分析.
主要成果:
- 该研究确定了接受化疗的915名患者,528名 (57%) 患有CIPN.
- 11个基因内的60个单核酸多态 (SNP),包括RCOR1,CLDN14,TRIM5和TMC2,达到了整个基因组的暗示意义.
- 在这个队列中,以前没有发现的与CIPN相关的SNP达到全基因组显著性.
结论:
- 这项研究表明新的基因组位置可能会影响CIPN的发展.
- 基于EHR的CIPN定义可以促进更大的样本大小,并增加遗传研究中的统计能力.
- 这些发现有助于了解CIPN的遗传基础,并可能为个性化治疗策略提供信息.
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