EMERGE PHASE III CLINICAL CENTER AT PARTNERS HEALTHCARE

PARTNERS HEALTHCARE 新兴三期临床中心

• 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
• 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

 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大型生物库、来自新英格兰最大的综合医疗保健提供商的超过 400 万名参与者的电子病历 (EMR) 中的临床数据、先进的生物信息学专业知识和最先进的遗传分析。我们提出三个目标。 (1) 目标 1. 发现。我们将测试这样一个假设：包含 50,000 个功能丧失 (LoF) 等位基因的定制芯片的常见和罕见变异将与源自 EMR 的心血管、神经精神和免疫介导的表型相关。目前，我们正在使用定制芯片对 25,000 个 Partners HealthCare Biobank 受试者进行基因分型，其中包括我们分析过的 63,000 个外显子组中的 LoF 等位基因。 (2) 目标 2. 外显率和多效性。我们将测试这样一个假设：对一组已建立的基因或基因座进行测序将使我们能够发现额外的变异，并使用 EMR 表型定义外显率和多效性。 eMERGE 网络选择的基因中的罕见变异将通过 PheWAS 和图表审查来研究外显率和多效性结果。此外，我们准备进行基因型召回研究，因为所有生物银行参与者都同意此类召回。 (3) 目标 3. 实施。我们将检验这样一个假设：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，从而为患者提供安全且具有成本效益的益处。我们将筛查整个生物样本库 我们对 25,000 名个体进行了 LDLR 基因的致病性变异检测，该基因是早发冠状动脉疾病的主要遗传原因，并进行了一项探索性试验来披露这一信息。具有 LDLR 致病性变异的生物样本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 确认，并且在一组中，这一结果 将通过 EMR 传达给他们的医生。在一年的时间里，我们将通过参与者调查和电子病历查询收集以下结果：医生就诊、实验室检测、药物处方变化、低密度脂蛋白水平、医疗费用以及因干预而接受筛查和治疗的家庭成员数量。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用于测序的基因的大规模实施方案中。最后，我们将参与所有网络活动，以促进遗传学进入临床实践。