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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：
8968123
负责人：
ELIZABETH W KARLSON
金额：
$ 97.24万
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 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8968123
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 Enrollment Family member Funding Genes Genetic Genomics 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 Medicine Mental Depression Mining Movement Multiple Sclerosis Mutation New England Newborn Infant Outcome Participant 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 arm base biobank clinical care clinical practice clinical sequencing clinically actionable cost cost effective design exome exome sequencing experience genetic analysis genetic information genetic variant hypercholesterolemia implementation research loss of function neuropsychiatry novel pilot trial pleiotropism premature public health relevance randomized trial rare variant tool

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.