EMERGE PHASE III CLINICAL CENTER AT PARTNERS HEALTHCARE

PARTNERS HEALTHCARE 新兴三期临床中心

基本信息

批准号：
9493516
负责人：
ELIZABETH W KARLSON
金额：
$ 95.32万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9493516
关键词：
Algorithms Alleles Area Asthma Attention deficit hyperactivity disorder Bioinformatics Biology Bipolar Disorder CTLA4 gene Callback Cardiovascular Diseases Cardiovascular system Clinical Clinical Data Clinical Trials Complex Computerized Medical Record Congestive Heart Failure Consent Coronary Arteriosclerosis Coronary heart disease Cost Effectiveness Analysis Custom DRD2 gene Data Disease Electronic Medical Records and Genomics Network Enrollment Family member Funding Genes Genetic Genomic medicine Genotype Goals HLA-DRB1 Health Personnel Healthcare Immune Individual Inflammatory Bowel Diseases Informatics Intervention LDL Cholesterol Lipoproteins LDLR gene Laboratories Learning Low-Density Lipoproteins Machine Learning Mediating Medical Care Costs Medicine Mental Depression Mining Movement Multiple Sclerosis Mutation New England Newborn Infant Outcome Participant Pathogenicity Patients Penetrance Pharmaceutical Preparations Pharmacogenetics Phase Phenotype Physicians Population Population Attributable Risks Protocols documentation Public Health Research Rheumatoid Arthritis Schizophrenia Source Stream Stroke Surveys TCF7L2 gene TNFRSF1A gene TYK2 Testing Variant Visit actionable mutation arm base biobank biomarker panel clinical care clinical practice clinical sequencing clinically actionable cost effective design exome experience genetic analysis genetic information genetic variant hypercholesterolemia implementation research loss of function neuropsychiatric disorder neuropsychiatry novel pilot trial pleiotropism premature public health relevance randomized trial rare variant support tools

项目摘要

DESCRIPTION (provided by applicant): The eMERGE III Clinical Center proposal from Partners HealthCare leverages a large biobank, clinical data in the electronic medical records (EMR) for >4 million participants from the largest integrated health care provider in New England, advanced bioinformatics expertise and state-of-the-art genetic analysis. We propose three aims. (1) Aim 1. Discovery. We will test the hypothesis that common and rare variants from a custom chip including 50,000 loss of function (LoF) alleles will be associated with cardiovascular, neuropsychiatric and immune-mediated phenotypes derived from the EMR. We are currently genotyping 25,000 Partners HealthCare Biobank subjects with a custom chip that includes LoF alleles from 63,000 exomes that we have analyzed. (2) Aim 2. Penetrance and Pleiotropy. We will test the hypothesis that sequencing a set of established genes or loci will allow us to discover additional variation, and define penetrance and pleiotropy using EMR phenotypes. Rare variants in genes selected by the eMERGE network will be studied for penetrance and pleiotropic outcomes by PheWAS and chart review. In addition, we are poised to perform recall-by-genotype studies because all Biobank participants have provided consent for such callback. (3) Aim 3. Implementation. We will test the hypothesis that physicians will alter their surveillance and treatment of patients based upon voluntary return of actionable variants to provide safe and cost-effective benefits to patients. We will screen our entire Biobank population of 25,000 individuals for pathogenic variants in the LDLR gene, the leading genetic cause of premature coronary artery disease, and conduct an exploratory trial in disclosing this information. Biobank participants with pathogenic variants in LDLR will be offered enrollment into a randomized trial, in which their finding will be CLIA-confirmed, and in one arm, this result will be communicated to their physicians through the EMR. Over one year, we will collect the following outcomes through participant surveys and EMR queries: physician visits, laboratory testing, changes in medication prescriptions, LDL levels, medical costs and the number of family members screened and treated as a result of the intervention. We will collaborate with the entire eMERGE III Network to incorporate what we learn from this pilot trial into large-scale implementation protocols for the genes selected by the Network for sequencing. Finally, we will participate in all Network activities to enhance the movement of genetics into clinical practice.

描述（由申请人提供）：Partners HealthCare 的 eMERGE III 临床中心提案利用了来自新英格兰最大的综合医疗保健提供商的超过 400 万参与者的大型生物库、电子病历 (EMR) 中的临床数据、先进的生物信息学专业知识我们提出三个目标： (1) 目标 1. 我们将测试来自定制芯片的常见和罕见变异，其中包括 50,000 个功能丧失。 (LoF) 等位基因将与源自 EMR 的心血管、神经精神和免疫介导的表型相关。我们目前正在使用定制芯片对 25,000 名 Partners HealthCare Biobank 受试者进行基因分型，其中包括我们分析过的 63,000 个外显子组的 LoF 等位基因。 2. 外显率和多效性我们将检验这样的假设：对一组已确定的基因或基因座进行测序将使我们能够发现额外的变异，并定义它们。使用 EMR 表型的外显率和多效性将通过 PheWAS 和图表审查来研究 eMERGE 网络选择的基因中的罕见变异，因为所有生物银行参与者都提供了外显率和多效性结果。 (3) 目标 3. 实施我们将检验这样的假设：医生将根据可操作变异的自愿返回来改变对患者的监测和治疗，以提供安全和有效的治疗。我们将对整个生物库进行筛选，为患者带来具有成本效益的好处。对 25,000 名个体中的 LDLR 基因的致病性变异（早发冠状动脉疾病的遗传主要原因）进行研究，并进行一项探索性试验来披露这一信息，生物库参与者将被纳入一项随机试验，其中。他们的发现将得到 CLIA 的证实，并且在一方面，这个结果将通过 EMR 传达给他们的医生在一年内，我们将通过调查和 EMR 查询收集以下参与者结果：医生就诊、实验室检测、药物处方变化、LDL 水平、医疗费用和接受筛查的家庭成员数量。我们将与整个 eMERGE III 网络合作，将我们从这次试点试验中学到的知识纳入网络选择的基因的大规模实施方案中进行测序。网络活动增强基因运动进入临床实践。