Better Outcomes for Children: GWAS & PheWAS in eMERGEII.

描述（由申请人提供）：辛辛那提儿童医院医学中心（CCHMC）和波士顿儿童医院（CHB）提议，儿科基因组和电子病历（EMR）研究联盟（PAGER）成为儿科机构eMERGE II期网络（RFA HG 11-022）的站点。我们计划使用相关的基因组和表型全关联研究（GWAS & PheWAS）数据进行持续的、可扩展的努力，以告知和改善个体儿童的护理。CCHMC和CHB卓越的教师和信息学基础设施已经实施了基于i2b2（整合生物学和床边的信息学）平台的中心范围的医疗保健工具，以“仪器企业基因组发现”。PAGER i2b2数据库包含250万份电子病历（所有住院和门诊病例），并以每年10万名新患者的速度增长。i2b2数据从Epic EMR和Cerner EMR上传，经过转换、去识别、增强研究和遗留临床数据，并链接到PAGER生物库和GWAS数据。此外，这两个机构正在实施雄心勃勃的生物库，目前包含150 000个样本，并将以每年100 000 000个样本的速度增加，这些样本来自有200 000个医疗记录的儿童。在Aim 1中，我们将在i2b2基础设施的基础上开发SHRINE，这将允许跨eMERGE II的表型标准化和数据共享。在目标2中，我们将提供6,861个病例，这些病例具有emr、DNA、GWAS数据和提交给dbGaP的机构认证，以及返回结果的路径。CHB和CCHMC学术院系的许多同事都是他们学术兴趣的表型倡导者，为表型算法的开发和GWAS和PheWAS在eMERGE II网络中的应用提供了多种可能性。我们将致力于并探索由eMERGE II指导委员会选择的以前和新的表型。在目标3和4中，我们将探讨对患者和对照组临床相关和偶然基因组发现的态度和使用。我们将利用为基因伙伴关系（TGP）实施的新型知情队列监督委员会（ICOB）的基础设施，制定一个全国性的流程，以解决围绕将研究成果返还给父母、参与者和照顾者的伦理问题。我们希望对标准程序达成共识做出重大贡献，以满足患者的期望和需求，并改善患者护理。最后，两家PAGER机构计划在支持eMERGE II的基础设施上进行重大投资，在未来五年内总计价值5000万美元，这将大大提高PAGER站点和eMERGE II的生产力。我们对加入eMERGE II非常感兴趣，因为它有望为CCHMC和CHB的使命做出贡献，这些使命是通过全面整合的全球方式改善儿童健康和改变护理方式

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.