Supporting Precision Medicine for Maternal and Pediatric Care through Pharmacogenomics Research

项目总结/摘要-项目1 药物基因组学领域已经从发现导致可变的遗传变异发展到了现在。 药物代谢酶的功能成为临床精准医学的基石。但有 有限的数据支持儿童和妇女在怀孕期间和怀孕后的药物基因关联。的 儿童和妊娠期的独特生理学需要在临床前验证药物基因组学信号 实施.这些知识差距对少数群体的个人来说更为严重，他们 基因组研究，特别是药物基因组学研究的代表性不足， 问题研究该项目的主要目标是推进研究和支持临床实施， 用于儿童和孕妇的药物基因组学。我们的工作将采用社区参与的方法：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， 电子健康记录表型分析; 3）识别和量化具有未知功能后果的变体 在不同的个人，以告知未来的研究工作和减少差异。目标1将评估 不同队列的慢性乙型肝炎儿童对药物基因组学检测的知识和态度 疾病和孕妇，在接受药物基因组学检测结果之前和之后。这个目标将开始 与社区参与工作室合作，以确定促进和加强儿童融入的战略， 慢性健康状况，孕妇，少数民族和药物基因组学残疾人 research.然后，我们将在药物基因组学检测和返回结果之前和之后进行调查。目的2 将利用我们庞大的生物库资源来验证女性中的高频药物-基因相互作用， 儿童，使这些人群的循证临床实施，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表型分析方法和工具， 完成目标，并促进我们网站和其他网站的未来研究。目标3将确定和量化遗传 在一个不同的研究中，儿童和孕妇中药物基因组学基因的未知功能变体 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童和青少年精确治疗的关键知识缺陷， 产妇人口。

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.