Integrative Analysis of a GWAS Repository with EMRs from over 40,000 Children

描述(由申请人提供)：费城儿童医院(CHOP)的应用基因组学(CAG)中心已经建立了一个儿科生物信息库，已有40,000多名儿童获准访问电子病历(EMR)，并进行更新和重新联系。所有研究对象都已在Infinium550HH、610Q、660Q(Illumina)或Affymetrix 6.0全基因组关联研究(GWAS)阵列上进行了基因分型。NHGRI于2007年启动了电子医疗记录和基因组学(Emerge)网络，以支持现有的生物信息库，以开发必要的方法和程序，以帮助来自EMR的表型和环境暴露的GWAS参与者。这一努力最近得到了扩大，现在正在将儿科研究调查员(PSI)与现有的生物信息库结合起来。鉴于我们建立的大规模数据集和资源，我们的CAG中心处于非常有利的地位，能够抓住这个机会。我们的主要目标是在Emerge计划的基础上，根据Emerge程序定义EMR的表型，并在共享EMR数据对患者隐私的风险最小的情况下进行Gwas，为研究的进行制定同意和社区咨询程序，并开始将基因组研究成果纳入临床护理。我们将与其他Emerge网络组织和NHGRI合作实现这些目标，扩大和纳入新的表型，目的是将GWA基因分型信息纳入EMR，试图改善临床护理。具体地说，在具体目标1中，我们将使用来自所有民族的40,000名0-21岁儿童的EMR，这些儿童已经在密集的GWAS阵列上进行了基因分型，以挖掘40多个表型的疾病表型和环境暴露数据，并与其他Emerge网站一起建立表型/基因数据库，用于未来的临床开发。我们还将挖掘EMR数据以确定药物遗传学(PGx)反应概况，包括疗效和不良事件，并在现有的儿科数据集中搜索影响常用药物反应变异的多态性。在具体目标2中，我们将延长我们基于阵列的临床细胞基因组计划中CLIA/CAP认证的工作流程状态，以支持未来与研究参与者共享遗传/基因组数据。在具体目标3中，我们将为CAG生物储存库和数据库建立与Emerge站点保持一致的指南和治理规则，并生成知情同意程序，以优化现有数据和样本用于研究，并与其他Emerge小组合作促进数据的临床实用。所有CHOP患者都在接受EMR，我们已经投入了大量资金来整合EMR和Gwas数据集，并将输出纳入我们认证的CAP/CLIA标准，以与Emerge计划的目标保持一致。因此，我们相信CAG处于非常有利的地位，可以为Emerge-II儿科网络做出贡献。

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 40,000 children who have been consented for access to electronic medical records (EMRs) with updates and recontact. All of the study subjects have been genotyped on either the Infinium 550HH, 610Q, 660Q (Illumina) or the Affymetrix 6.0 genome-wide association study (GWAS) arrays. NHGRI initiated the electronic medical records and genomics (eMERGE) Network in 2007 to support existing biorepositories to develop necessary methods and procedures to facilitate GWAS in participants with phenotypes and environmental exposures derived from EMRs. This effort was recently expanded and is now incorporating Pediatric Study Investigators (PSI) with existing biorepositories. Our CAG center is extremely well positioned for this opportunity given its large-scale dataset and resources we have built. Our primary objective is to build upon the eMERGE initiatives and define phenotypes from EMRs in accordance with eMERGE procedures and conduct GWAS with minimal risks to patient privacy from sharing of EMR data, and develop consent and community consultation procedures for conduct of research and begin incorporating genomic research results into clinical care. We will achieve these goals in collaboration with the other eMERGE network groups and the NHGRI to expand and incorporate new phenotypes with the intention of incorporating GWA genotyping information into EMRs in an attempt to improve clinical care. Specifically, in Specific Aim 1, we will use EMRs from >40,000 children of all ethnic groups, aged 0-21, already genotyped on dense GWAS arrays, to mine disease phenotypes and environmental exposure data in over 40 phenotypes and establish a phenotype/genotype database for future clinical development with other eMERGE sites. We will also mine EMR data to determine pharmacogenetic (PGx) response profiles, both efficacy and adverse events and search for polymorphisms impacting variation in response to commonly used drugs in the existing pediatric dataset. In Specific Aim 2, we will extend our CLIA/CAP certified workflow status in our array-based clinical cytogenomics program to enable future sharing of genetic/genomic data with the study participants. In Specific Aim 3, we will establish guidelines & governance rules for the CAG biorepository and databases in keeping with eMERGE sites, and generate informed consent procedures that optimize existing data and sample use for research and foster clinical utility of the data in collaboration with the other eMERGE groups. All CHOP patients are on EMR and we have invested significantly in integrating EMR and GWAS datasets and incorporating the outputs into our certified to CAP/CLIA standards, in keeping with the objectives of the eMERGE program. Thus, we believe CAG is exceptionally well positioned to contribute to the eMERGE-II Pediatric network.