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

基因组学医学在患者护理中的未来：CHOP 的贡献

• 批准号: 9902001
• 负责人: Hakon Hakonarson
• 金额: $ 86.65万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9902001
• 关键词: Adult; Adverse event; Algorithms; American; Asthma; Atopic Dermatitis; Attention deficit hyperactivity disorder; Catalogs; Child; Childhood; Clinical; Clinical Pathology; Clinical Trials; Complex; Consent; Data; Data Set; Databases; Development; Diabetes Mellitus; Disease; Drug usage; Early Intervention; Education; Electronic Health Record; Electronic Medical Records and Genomics Network; Environment; Epilepsy; Family; Future; Gastroesophageal reflux disease; Genetic; Genetic Polymorphism; Genomic medicine; Genomics; Genotype; Grant; Guidelines; Health; Healthcare; Individual; Informatics; Infrastructure; Institutional Review Boards; Intellectual functioning disability; Laboratories; Lead; Libraries; Medical; Metabolic syndrome; Obesity; Obstructive Sleep Apnea; Outcome; Parents; Participant; Pathologist; Patient Care; Patients; Pediatric Hospitals; Pediatric cohort; Pharmaceutical Preparations; Pharmacogenomics; Phase; Phenotype; Philadelphia; Physicians; Positioning Attribute; Preventive Intervention; Procedures; Process; Protocols documentation; Public Health; Publications; Quality Control; Research; Resources; Risk; Sampling; Series; Severities; Site; Surveys; Time; Translations; Update; Validation; Variant; Work; actionable mutation; analysis pipeline; autism spectrum disorder; autistic children; base; biobank; biomarker discovery; clinical care; clinical decision support; clinical diagnostics; clinically significant; college; cost effectiveness; data mining; density; disorder prevention; education resources; exome; experience; flexibility; genetic variant; genome sequencing; genome wide association study; genomic data; genomic tools; improved; novel; patient oriented; patient population; pediatric patients; programs; prospective; public health relevance; rare variant; response; success; tool; web site; whole genome

 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.

 描述（由申请人提供）：费城儿童医院（CHOP）的应用基因组中心（CAG）已建立了一个儿科生物座位，并同意有60,000多名儿童同意获得电子健康记录（EHR），并定期更新，重新接触，高密度基因组和高密度基因组范围内（GWA）（GWA）（GWA）。对于这个项目，我们提出了反映出现财团工作组机制的五个具体目标。这些将建立在Emerge II期间得出的实质性初步数据的基础上，其中一系列的GWA，测序，药物基因组学（PGX），EHR整合和回报率（ROR）项目有助于建立转化和Emerge III努力的平台。在这些目标的第一个目标中，我们建议继续扩大出现的表型库，并提出了四种铅表型：肥胖，癫痫，智力障碍和自闭症，其中我们在发现，整合和翻译方面都有很强的记录。在特定的目标2下，我们建议利用CAG作为基因组学研究的世界领导者的地位，以表征2,000名CAG患者的稀有变体，在那里我们已经在参与的附录中分类了数百种稀有变体。利用CAG和Emerge的这一资源和专业知识，我们建议将可行的发现归还至少约160个父母（特定目标3）。这项工作将建立在我们现有的ROR平台上，该平台在Emerge II期间建立，该平台将结果归还给了160名自闭症儿童的父母，以及数百名具有PGX风险概况的人。我们的第四个目标是评估ROR的健康影响，成本效益和ELSI的影响，我们旨在纵向跟踪以四个时间点返回结果的所有家庭，利用与儿科出现的合作伙伴一起开发的现有资源和调查。最后，我们提出了在Emerge II下建立的EHR整合的大规模扩展，该集成还为Emerge Network的患者和医疗专业人员提供并整合了教育资源。最终，我们预计这些努力的直接结果将改善CHOP患者的医疗保健，并扩展到整个Emerge Network。此外，我们凭借出现的合作伙伴，旨在建立一个蓝图，以使基因组学和EHR数据的整合，以至于它将具有真正改变美国医学实践的真正潜力。

项目成果

Outcomes of Returning Medically Actionable Genomic Results in Pediatric Research.

• DOI: 10.3390/jpm12111910
• 发表时间: 2022-11-16
• 期刊: Journal of personalized medicine
• 作者: Blumling AA;Prows CA;Harr MH;Chung WK;Clayton EW;Holm IA;Wiesner GL;Connolly JJ;Harley JB;Hakonarson H;McGowan ML;Miller EM;Myers MF
• 通讯作者: Myers MF

Association between high-risk disease loci and response to anti-vascular endothelial growth factor treatment for wet age-related macular degeneration.

• DOI: 10.1097/iae.0b013e31822a2c7c
• 发表时间: 2012-01
• 期刊: Retina (Philadelphia, Pa.)
• 作者: Orlin A;Hadley D;Chang W;Ho AC;Brown G;Kaiser RS;Regillo CD;Godshalk AN;Lier A;Kaderli B;Stambolian D
• 通讯作者: Stambolian D