Utilizing Polygenic Risk to Understand and Improve Outcomes: A Model For Overturning Health Disparities Through Minority-Enriched Genomics Healthcare

利用多基因风险来理解和改善结果：通过少数族裔丰富的基因组医疗保健推翻健康差异的模型

• 批准号: 10207724
• 负责人: Hakon Hakonarson
• 金额: $ 174.25万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10207724
• 关键词: Address; Adult; African; African American; Age of Onset; Area; Asthma; Autoimmune Diseases; Boston; Caring; Child; Childhood; Clinical; Collaborations; Communication; Communities; Coronary Arteriosclerosis; Crohn' s disease; Custom; Data; Data Set; Development; Diabetes Mellitus; Disease; Education; Educational Materials; Electronic Health Record; Electronic Medical Records and Genomics Network; Focus Groups; Genetic; Genetic Risk; Genomics; Genotype; Goals; Health; Health Personnel; Health Professional; Healthcare; Hyperlipidemia; Inflammatory Bowel Diseases; Information Centers; Infrastructure; Institutional Review Boards; Insulin-Dependent Diabetes Mellitus; Link; Lipids; Measures; Methodology; Minority; Minority Groups; Minority Recruitment; Modeling; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Outcome Assessment; Outcome Measure; Output; Parents; Participant; Pathway interactions; Patient Recruitments; Patient Self-Report; Patients; Pediatric Hospitals; Peer Review; Pennsylvania; Perception; Persons; Phenotype; Philadelphia; Precision Health; Precision therapeutics; Primary Health Care; Protocols documentation; Provider; Publications; Questionnaires; Randomized; Recommendation; Recording of previous events; Research; Rest; Risk; Risk Assessment; Risk Estimate; Risk Factors; Risk Management; Risk Reduction; Sampling; Secure; Sensitivity and Specificity; Severities; Severity of illness; Site; Testing; Underserved Population; United States; Universities; Validation; Work; base; biobank; cardiovascular disorder risk; care outcomes; chatbot; clinical decision support; clinical efficacy; clinical implementation; collaborative approach; design; ethical legal social implication; ethnic minority population; experience; genome-wide; health care delivery; health disparity; health disparity populations; improved; improved outcome; innovation; patient portal; polygenic risk score; programs; prospective; racial minority; recruit; repository; risk perception; risk variant; success; trait; uptake; whole genome; willingness

ABSTRACT This eMERGE-4 program is focused on generating and validating polygenic risk scores (PRS) for multiple phenotypes using multiple available datasets across the eMERGE network, followed by a site-specific implementation of PRS in 2,500 prospectively recruited patients we perform at The Children’s Hospital of Philadelphia and University of Pennsylvania. To address health disparities and underrepresentation of African Americans in genomic research, 75% (1,875) of participants will be of African ancestry. With capacity to pursue many others, we propose five principal phenotypes: asthma, diabetes (T1D/T2D); autoimmune disease, Crohn’s disease (CD); and hyperlipidemia with focus on coronary artery disease. Sensitivity, specificity, and clinical efficacy/impact with respect to improved healthcare delivery will be measured. We will work with eMERGE partners to develop a customized array that address inequities in traditional approaches, in particular, lack of PRS data in minorities. We will establish an enriched recruitment, engagement, and retention protocol that will include targeted recruitment, enhanced communication with participants and health care professionals, boosted analysis and EHR integration, and a dynamic education program focusing on AAs with an aim to decrease disparities in health by recruitment of minorities and improved health outcomes. The education program will be informed by an empirical collaboration with Boston Children’s Hospital, where we will examine ethical, legal, and social implications (ELSI) of return of genomic risk estimates, specifically differences in risk perception and willingness to participate in risk reduction recommendations based on how risk is framed, disease severity, age of onset, and actionability. Results will inform return of genomic risk estimates to all 2,500 participants, and assess healthcare outcomes across the key disease areas proposed. We will work with the consortium to delineate best practices for returning genomic risk estimates and create an innovative return of results protocol. Finally, we will integrate PRS and genomic risk estimates with patients’ electronic health records by leveraging Care Assistant, an innovative clinical decision support (CDS) framework developed at CHOP. We will create CDS integrated with the CHOP EHR and provider education in MyResults. In a cluster-randomized design using our primary-care research network, we will test the hypothesis that implementation of CDS will increase the uptake of risk reduction recommendations by both patients and providers compared to current EHR integration (EHRI).

摘要 该eMERGE-4计划的重点是生成和验证多基因风险评分（PRS）， 使用eMERGE网络中的多个可用数据集进行表型分析，然后进行特定地点的 在2,500例前瞻性招募的患者中实施PRS，我们在北京儿童医院进行 费城和宾夕法尼亚大学。解决健康差距和非洲人代表性不足问题， 在美国的基因组研究中，75%（1，875）的参与者将是非洲血统。有能力追求 我们提出了五种主要的表型：哮喘、糖尿病（T1 D/T2 D）、自身免疫性疾病、克罗恩病、 疾病（CD）;和高脂血症，重点是冠状动脉疾病。灵敏度、特异性和临床 将测量关于改进的医疗保健提供的功效/影响。我们将与eMERGE合作 合作伙伴制定一个定制的系列，解决传统方法中的不平等问题，特别是缺乏 少数民族的减贫战略数据。我们将建立一个丰富的招聘，参与和保留协议， 包括有针对性招募、加强与参与者和医护专业人员的沟通， 分析和EHR整合，以及一个动态的教育计划，重点是AA，旨在减少 通过招募少数民族和改善健康结果来消除健康差距。教育计划将是 根据与波士顿儿童医院的实证合作，我们将审查道德、法律的和 基因组风险估计回报的社会影响（ELSI），特别是风险认知的差异， 愿意参与基于风险框架、疾病严重程度、年龄 和可诉性。结果将告知所有2，500名参与者的基因组风险估计值， 评估拟议的关键疾病领域的医疗保健成果。我们将与财团合作， 描述返回基因组风险评估的最佳实践，并创建创新的结果返回协议。 最后，我们将整合PRS和基因组风险评估与患者的电子健康记录， Care Assistant是CHOP开发的一个创新的临床决策支持（CDS）框架。我们将创建 CDS与CHOP EHR集成，并在MyResults中提供教育。在一个随机分组设计中， 我们的初级保健研究网络，我们将测试的假设，实施CDS将增加 与当前的EHR集成相比，患者和提供者接受风险降低建议 （EHRI）。