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（由适用提供）：来自Partners Healthcare的Emerge III临床中心提案利用了大型生物库，电子病历中的临床数据（EMR）的临床数据（EMR），来自新英格兰最大的综合医疗保健提供商，高级生物信息信息学专业化和省级遗传分析的400万参与者。我们提出了三个目标。（1）目标1。发现。我们将检验以下假设：定制芯片中的常见和稀有变体（包括50,000个功能损失（LOF）等位基因）将与源自EMR得出的心血管，神经精神病学和免疫介导的表型有关。目前，我们正在基因分型25,000名合作伙伴医疗保健生物库受试者，其中包括我们已经分析的63,000个外来的LOF等位基因的定制芯片。（2）AIM 2。渗透率和多效性。我们将测试以下假设：对一组既定基因或局部的测序将使我们能够发现额外的变化，并使用EMR表型来定义渗透率和多效性。 Phewas和Chart Review将研究由Emerge网络选择的基因中的罕见变体以进行外渗和多效性结果。此外，由于所有生物库参与者都同意此类回调，因此我们被毒死了进行召回的研究。（3）目标3。实施。我们将检验以下假设：医生将根据自愿回报可行的变体来改变对患者的监视和治疗，以为患者提供安全且具有成本效益的益处。我们将筛选整个生物库 LDLR基因中有25,000名病原变异的人群是过早冠状动脉疾病的主要遗传原因，并在披露此信息时进行了探索性试验。 LDLR中具有致病性变异的生物库参与者将入学到随机试验中，在该试验中，他们的发现将被clia确认，并且在一个手臂中，此结果一年多来，我们将通过参与的调查和EMR查询来收集以下结果：身体就诊，实验室测试，药物处方的变化，LDL水平，医疗费用以及由于干预而被筛查和治疗的家庭成员人数。我们将与整个Emerge III网络合作，将我们从该试验试验中学到的知识纳入网络为测序网络选择的基因的大规模实施协议中。最后，我们将参加所有网络活动，以增强基因进入临床实践。