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

对 GWAS 存储库与 40,000 多名儿童的 EMR 进行综合分析

• 批准号: 8514179
• 负责人: Hakon Hakonarson
• 金额: $ 60万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-15 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8514179
• 关键词: Accreditation; Address; Adult; Adverse effects; Adverse event; American; Area; Authorization documentation; Back; Biological Markers; Catchment Area; Child; Childhood; Clinical; Clinical Medicine; Clinical Research; Collaborations; Computerized Medical Record; Consent; Data; Data Analyses; Data Set; Databases; Development; Diagnosis; Disease; Drug usage; Environment; Environmental Exposure; Ethnic group; Fostering; Future; Genetic; Genetic Polymorphism; Genomics; Genotype; Goals; Guidelines; Informed Consent; Intention; Knowledge; Laboratories; Methods; Mining; Minority; Mission; National Human Genome Research Institute; Output; Parents; Participant; Pathologist; Patient Care; Patients; Pediatric Hospitals; Pharmaceutical Preparations; Pharmacogenetics; Pharmacogenomics; Phenotype; Philadelphia; Population; Positioning Attribute; Practice Guidelines; Procedures; Rare Diseases; Recontacts; Recruitment Activity; Research; Research Personnel; Resources; Sampling; Site; Specificity; Study Subject; Translating; Update; Variant; Visit; Work; aged; base; biobank; clinical care; clinical practice; clinically relevant; college; community consultation; data mining; database of Genotypes and Phenotypes; disease phenotype; disorder risk; genome wide association study; improved; minimal risk; patient privacy; programs; repository; response; success; trait

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.

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) 建立了一个儿科生物存储库，其中包含 40,000 多名儿童，这些儿童已同意访问电子病历 (EMR)，并进行更新和重新联系。所有研究对象均已在 Infinium 550HH、610Q、660Q (Illumina) 或 Affymetrix 6.0 全基因组关联研究 (GWAS) 芯片上进行了基因分型。 NHGRI 于 2007 年启动了电子病历和基因组学 (eMERGE) 网络，以支持现有生物样本库开发必要的方法和程序，以促进具有来自 EMR 的表型和环境暴露的参与者的 GWAS。这项工作最近得到了扩展，目前正在将儿科研究调查员 (PSI) 与现有的生物样本库结合起来。鉴于我们建立的大规模数据集和资源，我们的 CAG 中心非常适合抓住这一机会。我们的主要目标是建立在 eMERGE 计划的基础上，根据 eMERGE 程序定义 EMR 的表型，并在共享 EMR 数据对患者隐私造成最小风险的情况下进行 GWAS，并制定研究进行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 网络团体和 NHGRI 合作实现这些目标，以扩展和纳入新表型，旨在将 GWA 基因分型信息纳入 EMR，以改善临床护理。具体来说，在具体目标 1 中，我们将使用超过 40,000 名各族裔 0-21 岁儿童的 EMR（已在密集 GWAS 阵列上进行基因分型）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，以便与其他 eMERGE 站点进行未来的临床开发。我们还将挖掘 EMR 数据，以确定药物遗传学 (PGx) 反应概况、疗效和不良事件，并在现有儿科数据集中寻找影响常用药物反应变化的多态性。在具体目标 2 中，我们将在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，以便将来能够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 生物样本库和数据库制定与 eMERGE 站点保持一致的指南和治理规则，并生成知情同意程序，以优化现有数据和研究样本使用，并与其他 eMERGE 小组合作促进数据的临床应用。所有 CHOP 患者均接受 EMR，我们投入了大量资金来整合 EMR 和 GWAS 数据集，并将输出纳入经过 CAP/CLIA 标准认证的产品中，以符合 eMERGE 计划的目标。因此，我们相信 CAG 非常有能力为 eMERGE-II 儿科网络做出贡献。