Better Outcomes for Children: GWAS & PheWAS in eMERGEII.

描述（由申请方提供）：辛辛那提儿童医院医学中心（CCHMC）和波士顿儿童医院（CHB）提议，基因组和电子病历（EMR）研究儿科联盟（PAGER）成为儿科机构eMERGE II期网络（RFA HG 11-022）的研究中心。我们计划进行一项持续的、可扩展的努力，利用相关的基因组和表型组关联研究（GWAS和PheWAS）数据，为个体儿童提供信息和改善护理。CCHMC和CHB的非凡教师和信息学基础设施已经实施了中心范围的医疗保健工具，以基于i2 b2（整合生物学和床边信息学）平台“为企业进行基因组发现提供工具”。PAGER i2 b2数据库包含250万例EMR（所有住院和门诊就诊），每年新增患者超过10万例。i2 b2数据从Epic EMR和Cerner EMR上传，经过转换、去识别、使用研究和遗留临床数据进行增强，并链接到PAGER生物储存库和GWAS数据。此外，这两个机构都在实施雄心勃勃的生物储存库，现在包含超过15，000个样本，每年将从具有i2 b2医疗记录的儿童中增加超过30，000个DNA样本。在目标1中，我们将在i2 b2基础设施的基础上开发SHRINE，这将允许在eMERGE II中实现表型标准化和数据共享。在目标2中，我们将贡献6，861个案例，这些案例具有EMR，DNA，GWAS数据和机构认证，以提交给dbGaP，以及返回结果的路径。CHB和CCHMC学术系的许多同事都是其学术兴趣表型的倡导者，为eMERGE II网络的GWAS和PheWAS的表型算法开发和应用提供了多种可能性。我们将为eMERGE II指导委员会选择的先前和新表型做出贡献并进行探索。在目标3和4中，我们将探讨患者和对照组对临床相关和偶然基因组发现的态度和使用。我们将利用我们为基因伙伴关系（TGP）实施的新型知情队列监督委员会（ICOB）的基础设施，制定一个国家程序，以解决围绕将研究结果返还给父母，参与者和护理人员的伦理问题。我们希望能为达成标准程序的共识做出重大贡献，以满足患者的期望和需求，并改善患者护理。最后，这两个PAGER机构计划对支持eMERGE II的基础设施进行重大投资，在今后五年内总价值超过50，000，000美元，这将大大提高PAGER网站和eMERGE II的生产力。我们对加入eMERGE II的极大兴趣源于其对CCHMC和CHB使命的预期贡献，这些使命是通过全面整合的全球性服务来改善儿童健康并改变护理服务。 公认的研究、教育和创新。

DESCRIPTION (provided by applicant): Cincinnati Children's Hospital Medical Center (CCHMC) and Children's Hospital Boston (CHB) propose that the Pediatric Alliance for Genomic and Electronic Medical Record (EMR) Research (PAGER) becomes a site for the eMERGE Phase II network for pediatric institutions (RFA HG 11-022). We plan a sustained, scalable effort to inform and improve the care of the individual child using relevant genome and phenome wide association study (GWAS & PheWAS) data. The extraordinary faculty and informatics infrastructure of CCHMC & CHB has implemented center-wide healthcare tools to "instrument the enterprise for genomic discovery" based on the i2b2 (Informatics for Integrating Biology and the Bedside) platform. The PAGER i2b2 databases contain 2.5 million EMRs (all inpatient and outpatient visits) and grow by >100,000 new patients per year. The i2b2 data are uploaded from the Epic EMR and Cerner EMR, transformed, de-identified, augmented with research and legacy clinical data, and linked to the PAGER biorepositories and GWAS data. In addition, both institutions are in the process of implementing ambitious biorepositories that now contain >15,000 samples and will grow at >30,000 DNA specimens per year from children with i2b2 medical records. In Aim 1 we will build on our i2b2 infrastructure to develop SHRINE, which will allow phenotypic standardization and data sharing across eMERGE II. In Aim 2 we will contribute 6,861 cases that have EMRs, DNA, GWAS data, and institutional certification for submission to dbGaP, as well as a path to return results. Many colleagues in the academic faculties at both CHB and CCHMC are advocates for phenotypes of their scholarly interest, providing a multitude of possibilities for phenotype algorithm development and application of GWAS and PheWAS for the eMERGE II network. We will contribute to and explore the previous and new phenotypes selected by the eMERGE II Steering Committee. In Aims 3 and 4 we will explore the attitudes towards, and use of, clinically relevant and incidental genomic findings in patient and control groups. We will utilize the infrastructure of our novel Informed Cohort Oversight Board (ICOB), implemented for The Gene Partnership (TGP), to develop a national process to address the ethical issues surrounding the return of research results to parents, participants, and caregivers. We hope to contribute significantly toward a consensus for standard procedures that fulfill patient expectations and needs, and that improve patient care. Finally, the two PAGER institutions plan major investments in the infrastructure supporting eMERGE II, valued at >$50,000,000 in aggregate over the next five years, which will greatly enhance the productivity of the PAGER site and eMERGE II. Our great interest in joining eMERGE II derives from its anticipated contributions toward the missions of CCHMC and CHB, which are to improve child health and transform delivery of care through fully integrated, globally recognized research, education, and innovation.