The Future of Genomics Medicine in Patient Care: Contributions from CHOP

 描述（由申请人提供）：费城儿童医院（CHOP）的应用基因组学中心（CAG）已经建立了一个儿科生物储存库，超过60，000名儿童同意访问电子健康记录（EHR），定期更新，重新联系和高密度全基因组关联（GWA）阵列数据。对于这个项目，我们提出了五个具体目标，反映了eMERGE联盟的可持续发展机制。这些将建立在eMERGE II期间获得的实质性初步数据的基础上，其中一系列GWA，测序，药物基因组学（PGx），EHR整合和结果返回（RoR）项目帮助建立了一个转化和eMERGE III工作的平台。在第一个目标中，我们建议继续扩大eMERGE表型库，并提出四种主要表型：肥胖，癫痫，智力残疾和自闭症，我们在发现，整合和翻译方面有很好的记录。在具体目标2下，我们建议利用CAG作为基因组学研究世界领导者的地位来描述2，000名CAG患者的罕见变异，我们已经在随附的附录中对数百种罕见变异进行了编目。利用CAG和eMERGE的这一资源和专业知识，我们建议将可操作的结果返回给至少约160名父母（具体目标3）。这项工作将建立在我们在eMERGE II期间建立的现有RoR平台上，该平台将结果返回给160名患有自闭症的CHOP儿童的父母，以及数百名具有PGx风险特征的个体。我们的第四个目标是评估RoR的健康影响，成本效益和ELSI影响，我们的目标是纵向跟踪在四个时间点返回结果的所有家庭，利用现有资源和与儿科eMERGE合作伙伴开发的调查。最后，我们建议大规模扩展我们的EHR集成，在eMERGE II下建立，它还为eMERGE网络中的患者和医疗专业人员提供和集成教育资源。最终，我们预计这些努力的直接结果将是改善CHOP患者的医疗保健，并扩展到整个eMERGE网络。此外，与我们的eMERGE合作伙伴一起，我们的目标是建立一个整合基因组学和EHR数据的蓝图，其规模将具有从根本上改变美国医疗实践的真实的潜力。

 DESCRIPTION (provided by applicant): The Center for Applied Genomics (CAG) at The Children's Hospital of Philadelphia (CHOP) has established a pediatric biorepository with over 60,000 children consented for access to electronic health records (EHRs) with regular updates, re-contact, and high-density genome-wide association (GWA) array data. For this project, we have proposed five specific aims reflecting the workgroup mechanism of the eMERGE consortium. These will build upon substantive Preliminary Data derived during eMERGE II, where a series of GWA, sequencing, pharmacogenomics (PGx), EHR integration, and return-of-results (RoR) projects helped establish a platform for translational and eMERGE III efforts. In the first of these aims, we propose to continue to expand the eMERGE phenotype library and we propose four lead phenotypes: obesity, epilepsy, intellectual disability, and autism, in which we have a strong record in discovery, integration, and translation. Under specific aim 2, we propose to leverage CAG's position as a world-leader in genomics research to characterize rare variants in 2,000 CAG patients, where we have already catalogued several hundred rare variants in the accompanying Appendix. Leveraging this resource and expertise at CAG and eMERGE, we propose to return actionable findings to a minimum of ~160 parents (Specific Aim 3). This effort will build upon our existing RoR platform established during eMERGE II that returned results to parents of 160 CHOP children with autism, and to several hundred individuals with PGx risk profiles. Our fourth aim is to evaluate the health impact, cost-effectiveness and ELSI implications of RoR, and we aim to longitudinally track all families to whom results are returned at four time-points, leveraging existing resources and surveys developed with pediatric eMERGE partners. Finally, we propose a massive expansion of our EHR integration, established under eMERGE II, which also provide and integrate education resources for patients and medical professionals across the eMERGE network. Ultimately, we anticipate that the immediate outcome of these efforts will be improved healthcare for patients at CHOP and expanding to the entire eMERGE network. Further, with our eMERGE partners, we aim to establish a blueprint for integrating genomics and EHR data on such a scale that it will have real potential to fundamentally change medical practice in the US.