Supporting Precision Medicine for Maternal and Pediatric Care through Pharmacogenomics Research

项目摘要/摘要--项目1 药物基因组学领域从发现引起变异的遗传变异开始取得进展。 药物代谢酶的作用是临床精准医学的基石。然而，有一些 支持儿童和妇女在怀孕期间和之后的药物基因关联的数据有限。这个 儿童和妊娠的独特生理学要求在临床之前对药物基因组信号进行验证 实施。对于来自少数族裔人口的个人来说，这些知识差距更加严重，他们 基因组研究，特别是药物基因组学研究的代表性不足，因此服务不足 学习。该项目的主要目标是推进研究并支持临床实施 儿童和孕妇的药物基因组学。我们的工作将使用社区参与的方法来：1) 阐明药物基因组学的知识、态度和优先事项；2)验证药物基因组学 使用创新和可推广的战略的儿科和孕产妇人口协会 电子健康记录表型分析；3)识别和量化功能后果未知的变异 在不同的个人中进行研究，以便为今后的研究工作提供信息，并减少差异。目标1将评估 不同人群慢性阻塞性肺疾病儿童药物基因组学检测知识和态度调查 疾病和孕妇在接受药物基因组学检测结果前后进行比较。这一目标将开始 通过社区参与工作室确定促进和促进有以下问题的儿童的融入的战略 慢性健康状况、孕妇、少数民族和药物基因组学残障人士 研究。然后，我们将在药物基因组测试和结果返回之前和之后进行调查。目标2 将利用我们的大型生物库资源来验证女性和 儿童能够对这些人群进行循证临床实施，并确定新的信号 进一步研究。这一目标将产生电子健康记录的表型方法和工具，以有效地 在我们的网站和其他网站上完成目标并促进未来的研究。目标3将识别和量化基因 儿童和孕妇药物基因组基因中未知功能的变异 生物库参与者的队列，告知需要表征的基因组多样性的谱。总的来说， 实现这些目标将解决儿科和妇科精准治疗的关键知识不足问题 母体人口。

PROJECT SUMMARY / ABSTRACT - PROJECT 1 The field of pharmacogenomics has progressed from the discovery of genetic variants that cause variable function of drug metabolism enzymes to a cornerstone of clinical precision medicine. However, there are limited data supporting drug-gene associations for children and for women during and after pregnancy. The unique physiology of childhood and pregnancy demand validation of pharmacogenomic signals prior to clinical implementation. These knowledge gaps are compounded for individuals from minority populations, who have been underrepresented and thus underserved by genomic research and specifically pharmacogenomic studies. The primary objective of this project is to advance research and support clinical implementation in pharmacogenomics for children and pregnant women. Our work will use a community engaged approach to: 1) illuminate knowledge of, attitudes about, and priorities for pharmacogenomics; 2) validate pharmacogenomic associations for pediatric and maternal populations using the innovative and generalizable strategy of electronic health records phenotyping; 3) identify and quantify variants with unknown functional consequence in diverse individuals in order to inform future research efforts and reduce disparities. Aim 1 will assess the knowledge and attitudes regarding pharmacogenomic testing among diverse cohorts of children with chronic disease and pregnant women, before and after receiving pharmacogenomic test results. This aim will begin with a Community Engagement Studio to identify strategies to facilitate and enhance inclusion of children with chronic health conditions, pregnant women, minorities, and those with disabilities in pharmacogenomic research. We will then perform surveys before and after pharmacogenomic testing and return of results. Aim 2 will leverage our large biobank resource to validate high-frequency drug-gene interactions in women and children to enable evidence-based clinical implementation for these populations and identify novel signals for further study. This aim will generate electronic health records phenotyping methods and tools to efficiently complete the aim and facilitate future research at our site and others. Aim 3 will identify and quantify genetic variants of unknown function in pharmacogenomic genes among children and pregnant women in a diverse cohort of biobank participants, informing the spectrum of genomic diversity requiring characterization. Overall, accomplishing these aims will address critical knowledge deficits for precision therapeutics for pediatric and maternal populations.