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疗中心 (CCHMC) 和波士顿儿童医院 (CHB) 建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 期网络的站点 (RFA HG 11-022)。我们计划开展持续、可扩展的工作，利用相关的基因组和表型组广泛关联研究（GWAS 和 PheWAS）数据来告知和改善对个别儿童的护理。 CCHMC 和 CHB 卓越的师资力量和信息学基础设施已实施了中心范围内的医疗保健工具，以基于 i2b2（整合生物学和床边的信息学）平台“为企业提供基因组发现工具”。 PAGER i2b2 数据库包含 250 万条 EMR（所有住院和门诊就诊），并且每年新增患者数量超过 100,000 名。 i2b2 数据从 Epic EMR 和 Cerner EMR 上传，经过转换、去识别化、通过研究和遗留临床数据进行增强，并链接到 PAGER 生物存储库和 GWAS 数据。此外，两家机构正在实施雄心勃勃的生物样本库，目前包含超过 15,000 个样本，并且每年将增加超过 30,000 个来自具有 i2b2 医疗记录的儿童的 DNA 样本。在目标 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 进行表型标准化和数据共享。在目标 2 中，我们将贡献 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 学术界的许多同事都是他们学术兴趣的表型的倡导者，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的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。我们将利用为基因合作伙伴关系 (TGP) 实施的新型知情群体监督委员会 (ICOB) 的基础设施，制定一个国家流程，以解决围绕将研究结果返还给父母、参与者和照顾者的伦理问题。我们希望为满足患者期望和需求并改善患者护理的标准程序达成共识做出重大贡献。最后，两个 PAGER 机构计划在未来五年内对支持 eMERGE II 的基础设施进行重大投资，总价值超过 50,000,000 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 的极大兴趣源于其对 CCHMC 和 CHB 使命的预期贡献，这些使命是通过完全一体化的全球一体化来改善儿童健康并改变护理服务的提供方式 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.