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).

抽象的 该 eMERGE-4 计划专注于生成和验证多个基因的多基因风险评分 (PRS) 使用 eMERGE 网络上的多个可用数据集来确定表型，然后是特定于站点的 我们在儿童医院对 2,500 名前瞻性招募的患者实施了 PRS 费城和宾夕法尼亚大学解决非洲人的健康差距和代表性不足问题 在美国人的基因组研究中，75%（1,875）的参与者将具有非洲血统。 对于许多其他疾病，我们提出了五种主要表型：哮喘、糖尿病（T1D/T2D）、自身免疫性疾病、克罗恩病； 疾病（CD）；和高脂血症，重点关注冠状动脉疾病。 我们将与 eMERGE 合作，衡量改善医疗服务的功效/影响。 合作伙伴开发定制阵列，解决传统方法中的不平等问题，特别是缺乏 我们将建立一个丰富的招募、参与和保留协议，以获取少数族裔的 PRS 数据。 包括有针对性的招募、加强与医疗保健专业人员的沟通、 分析和 EHR 整合，以及以 AA 为重点的动态教育计划，旨在减少 通过招募少数族裔来消除健康差异并改善健康结果。 通过与波士顿儿童医院的实证合作，我们将审查伦理、法律和 基因组风险估计返回的社会影响（ELSI），特别是风险认知和风险认知的差异 愿意根据风险的界定方式、疾病严重程度、年龄参与降低风险的建议 结果将通知所有 2,500 名参与者返回基因组风险评估，以及 我们将与该联盟合作评估拟议的关键疾病领域的医疗保健结果。 描述返回基因组风险估计的最佳实践，并创建创新的结果返回协议。 最后，我们将利用 PRS 和基因组风险评估与患者的电子健康记录相结合 Care Assistant，我们将创建 CHOP 开发的创新临床决策支持 (CDS) 框架。 CDS 与 MyResults 中的 CHOP EHR 和提供者教育相集成，采用集群随机设计。 我们的初级保健研究网络中，我们将检验 CDS 的实施将增加 与当前的 EHR 集成相比，患者和提供者都采纳了降低风险的建议 （EHRI）。