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

基本信息

批准号：
8719415
负责人：
Hakon Hakonarson
金额：
$ 18万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
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/8719415
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

项目摘要

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）已建立了一个儿科生物座席，拥有超过40,000名儿童，他们已同意使用更新和重新接触电子病历（EMRS）。所有研究受试者均已在Infinium 550HH，610Q，660Q（Illumina）或Affymetrix 6.0全基因组协会研究（GWAS）阵列上进行了基因分型。 NHGRI在2007年启动了电子病历和基因组学（Emerge）网络，以支持现有的生物膜效应，以开发必要的方法和程序，以促进具有EMR的表型和环境暴露的参与者中的GWA。这项工作最近扩大了，现在正在将小儿研究研究者（PSI）与现有的生物库融合在一起。鉴于我们已经建立的大规模数据集和资源，我们的CAG中心非常适合这个机会。我们的主要目标是基于出现的计划，并根据EMRES的程序来定义EMR的表型，并根据EMR数据共享EMR数据的隐私，并开发研究并开始将基因组研究结果纳入临床护理中的同意和社区咨询程序。我们将与其他Emerge网络组和NHGRI合作实现这些目标，以扩展和纳入新的表型，目的是将GWA基因分型信息纳入EMR，以试图改善临床护理。具体而言，在特定的目标1中，我们将使用已在密集的GWAS阵列上基因分型的所有种族的40,000名儿童中使用EMR来挖掘40多个表型中的疾病表型和环境暴露数据，并建立一个表型/基因型数据库，以与其他Emerge Sites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）响应概况，疗效和不良事件，并寻找影响现有儿科数据集中常用药物的差异的多态性。在特定目标2中，我们将在基于阵列的临床细胞基因组学计划中扩展我们的CLIA/CAP认证工作流程状态，以使未来与研究参与者共享遗传/基因组数据。在特定的目标3中，我们将针对CAG生物库和数据库建立指南和治理规则，以与出现的站点保持一致，并生成知情同意程序，以优化现有数据和样本使用，以与其他Emerge组协作进行研究和培养数据的临床实用性。所有CHOP患者都在EMR上，我们已经在集成EMR和GWAS数据集并将输出纳入我们的CAP/CLIA标准的认证方面进行了大量投资，这与Emerge计划的目标保持一致。因此，我们认为CAG在出色的II小儿网络中做出了良好的贡献。

项目成果

期刊论文数量（33）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

CYP2B6*6 or Not CYP2B6*6-That Remains a Question for Precision Medicine and Ketamine!

CYP2B6*6 或不是 CYP2B6*6——这对于精准医学和氯胺酮来说仍然是一个问题！

DOI：
10.1097/aln.0000000000001399
发表时间：
2016
期刊：
Anesthesiology
影响因子：
8.8
作者：
Cook-Sather,ScottD;Adamson,PeterC;Li,Jin;Hakonarson,Hakon
通讯作者：
Hakonarson,Hakon

Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A.

DOI：
10.1093/brain/awt233
发表时间：
2013-10
期刊：
Brain : a journal of neurology
影响因子：
0
作者：
Kasperaviciute D;Catarino CB;Matarin M;Leu C;Novy J;Tostevin A;Leal B;Hessel EV;Hallmann K;Hildebrand MS;Dahl HH;Ryten M;Trabzuni D;Ramasamy A;Alhusaini S;Doherty CP;Dorn T;Hansen J;Krämer G;Steinhoff BJ;Zumsteg D;Duncan S;Kälviäinen RK;Eriksson KJ;Kantanen AM;Pandolfo M;Gruber-Sedlmayr U;Schlachter K;Reinthaler EM;Stogmann E;Zimprich F;Théâtre E;Smith C;O'Brien TJ;Meng Tan K;Petrovski S;Robbiano A;Paravidino R;Zara F;Striano P;Sperling MR;Buono RJ;Hakonarson H;Chaves J;Costa PP;Silva BM;da Silva AM;de Graan PN;Koeleman BP;Becker A;Schoch S;von Lehe M;Reif PS;Rosenow F;Becker F;Weber Y;Lerche H;Rössler K;Buchfelder M;Hamer HM;Kobow K;Coras R;Blumcke I;Scheffer IE;Berkovic SF;Weale ME;UK Brain Expression Consortium;Delanty N;Depondt C;Cavalleri GL;Kunz WS;Sisodiya SM
通讯作者：
Sisodiya SM

Common variation contributes to the genetic architecture of social communication traits.

DOI：
10.1186/2040-2392-4-34
发表时间：
2013-09-18
期刊：
Molecular autism
影响因子：
6.2
作者：
St Pourcain B;Whitehouse AJ;Ang WQ;Warrington NM;Glessner JT;Wang K;Timpson NJ;Evans DM;Kemp JP;Ring SM;McArdle WL;Golding J;Hakonarson H;Pennell CE;Smith GD
通讯作者：
Smith GD

Pain versus analgesia: TAOK3 as a pharmacogene.

疼痛与镇痛：TAOK3 作为药物基因。