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）的应用基因组学中心（CAG）已经建立了一个儿科生物库，其中有超过40,000名儿童已经同意访问电子医疗记录（emr），并进行更新和重新联系。所有受试者均使用Infinium 550HH、610Q、660Q （Illumina）或Affymetrix 6.0全基因组关联研究（GWAS）阵列进行基因分型。NHGRI于2007年启动了电子医疗记录和基因组学（eMERGE）网络，以支持现有的生物储存库开发必要的方法和程序，以促进具有电子病历引起的表型和环境暴露的参与者的GWAS。这项工作最近得到了扩大，现在正在将儿科研究调查员（PSI）与现有的生物储存库结合起来。鉴于我们已经建立的大规模数据集和资源，我们的CAG中心在这个机会上处于非常有利的地位。我们的主要目标是建立在eMERGE计划的基础上，根据eMERGE程序从EMR中定义表型，并在共享EMR数据对患者隐私造成最小风险的情况下进行GWAS，并为开展研究制定同意和社区咨询程序，并开始将基因组研究结果纳入临床护理。我们将与其他eMERGE网络小组和NHGRI合作实现这些目标，扩大和纳入新的表型，意图将GWA基因分型信息纳入emr，以改善临床护理。具体而言，在Specific Aim 1中，我们将使用来自所有种族、年龄在0-21岁、已经在密集GWAS阵列上进行基因分型的40000名儿童的emr，来挖掘40多种表型的疾病表型和环境暴露数据，并建立表型/基因型数据库，用于未来与其他eMERGE站点的临床开发。我们还将挖掘EMR数据，以确定药物遗传（PGx）反应概况，包括疗效和不良事件，并在现有儿科数据集中搜索影响对常用药物反应变化的多态性。在具体目标2中，我们将在我们基于阵列的临床细胞基因组学项目中扩展我们的CLIA/CAP认证工作流程状态，以便将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生物库和数据库建立与eMERGE站点保持一致的指导方针和治理规则，并生成知情同意程序，优化现有数据和样本的研究使用，并与其他eMERGE小组合作促进数据的临床应用。所有CHOP患者都在进行EMR，我们在整合EMR和GWAS数据集方面投入了大量资金，并将输出纳入我们经CAP/CLIA认证的标准，以符合eMERGE计划的目标。因此，我们相信CAG在为emerging - ii儿科网络做出贡献方面处于非常有利的地位。

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.