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)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阶段II网络的站点(RFA HG 11-022)。我们计划一项持续的、可扩展的努力，利用相关的基因组和表型广谱关联研究(GWAS&Phewas)数据来通知和改善对单个儿童的护理。CCHMC和CHB卓越的教师和信息学基础设施实施了中心范围的医疗工具，以i2b2(整合生物学和床边的信息)平台为基础，为企业的基因组发现提供工具。寻呼机i2b2数据库包含250万急诊患者(所有住院和门诊就诊)，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、去身份识别、使用研究和遗留临床数据进行扩充，并链接到寻呼机生物信息库和Gwas数据。此外，这两家机构都在实施雄心勃勃的生物信息库，目前包含1.5万份样本，每年将增加3万份来自有i2b2病史儿童的DNA样本。在目标1中，我们将在我们的i2b2基础设施的基础上开发Shreine，这将允许表型标准化和跨Emerge II的数据共享。在目标2中，我们将贡献6861个拥有EMR、DNA、Gwas数据和机构认证的案例提交给DBGaP，以及一条返回结果的途径。CHB和CCHMC学院的许多同事都是他们学术兴趣的表型的倡导者，为表型算法的开发和在Emerge II网络中应用GWAs和PheWAs提供了多种可能性。我们将对Emerge II指导委员会选出的以前的和新的表型做出贡献和探索。在目标3和4中，我们将探索患者和对照组对临床相关和偶然的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，制定一个全国性的程序，以解决围绕向父母、参与者和照顾者返还研究成果的伦理问题。我们希望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，这两家寻呼机机构计划在未来五年对支持Emerge II的基础设施进行重大投资，总价值为5,000万美元，这将极大地提高寻呼机站点和Emerge II的生产率。我们对加入Emerge II的极大兴趣来自于它对CCHMC和CHB的预期贡献，这些使命是通过完全整合的全球范围内改善儿童健康和改变保健提供。 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.