Northwestern Genomic Risk Assessment and Management Program

西北基因组风险评估和管理计划

• 批准号: 10640230
• 负责人: REX L CHISHOLM
• 金额: $ 112.86万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 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/10640230
• 关键词: Adherence; Area; Behavior; Behavioral; Cardiovascular Diseases; Clinical; Collection; Communication; Communication Tools; Community Hospitals; Community Networks; Computerized Medical Record; DNA; Data; Deposition; Diagnosis; Disease; Educational Materials; Electronic Health Record; Electronic Medical Records and Genomics Network; Electronics; Enrollment; Ensure; Epidemiology; Ethnic Population; Family; Family history of; Genes; Genetic; Genetic Risk; Genomic medicine; Genomics; Genotype; Goals; Health system; Healthcare; Individual; Informatics; Information Technology; Infrastructure; Intervention; Knowledge; Leadership; Link; Malignant Neoplasms; Medical; Medical center; Medicine; Monitor; Morbidity - disease rate; Outcome; Participant; Patient Education; Patients; Performance; Persons; Pharmacogenomics; Phase; Phenotype; Pilot Projects; Population; Population Genetics; Population Heterogeneity; Positioning Attribute; Provider; Publishing; Recording of previous events; Research Personnel; Risk; Risk Assessment; Risk Estimate; Risk Management; Role; Site; Specific qualifier value; Symptoms; Techniques; Testing; Trust; age group; alternative communication; biobank; care outcomes; clinical care; clinical decision support; clinical decision-making; clinical implementation; community clinic; data warehouse; disorder risk; ethical, legal, and social implication; ethnic diversity; ethnic minority; expectation; experience; health disparity; health management; high risk; improved; innovation; mortality; novel; participant retention; polygenic risk score; prevent; programs; racial diversity; racial minority; racial population; rare variant; recruit; smartphone application; socioeconomics; success; theories; uptake

Summary Polygenic risk scores have the potential to change management for common diseases. However, concerns exist about the clinical implementation of PRS including the likely decreased performance of PRS in non-white populations and the need to develop improved communication and extended informatics support for use of the PRS in health care decisions. At Northwestern we will address these concerns through three major scientific questions related to the clinical use of PRS: 1) Does use of PRS contribute to improved adherence to risk management strategies and improved clinical outcomes? 2) Does a high risk PRS presented with culturally sensitive and tailored risk communication improve adherence and outcomes across diverse racial and ethnic groups? 3) Can we develop and test information technology that stores PRS in the EHR and delivers clinical decision support (CDS) to aid providers in PRS use clinically? To enable recruitment, retention, and outcome monitoring, we will create and then disseminate a smartphone application across Northwestern and, as possible, the Electronic Medical Records and Genomics (eMERGE) network to facilitate the goals of eMERGE 4 (e4). Northwestern has been a primary contributor to all phases of eMERGE with Northwestern investigators holding key leadership roles in the network. Northwestern’s previous rich experience in electronic phenotyping involves using information extracted from our enterprise data warehouse, along with genomics and epidemiology expertise in many areas, including PRS, for genomic discovery projects. We have a demonstrated ability to recruit and retain large and ethnically diverse clinical populations for genetic result return, and repeated successful integration of genetic results into Northwestern’s electronic health record as discrete, computable lab values enabling effective clinical decision support. We will employ innovative enrollment techniques that have higher success rates in diverse populations. As participants in the e4 consortium we will implement a program called ENDORSED (eMERGE Northwestern Develops Optimized Risk Scores for Everyone’s DNA). Through the following aims ENDORSED will assess the utility of PRS, including in diverse populations. In Aim 1, we will calculate and validate PRS for common disorders selected specifically because they have medically-actionable outcomes. Aim 2 will recruit 2500 subjects for participation in eMERGE 4, taking advantage of Northwestern Medicine’s extensive clinical network. Aim 3 will use behavior theory to create culturally sensitive communication tools and then integrate PRS data into the electronic health record. Aim 4 will then examine outcomes and uptake of behaviors before and after PRS return. The completion of these aims will assess and evaluate PRS use for common diseases in diverse groups producing important data about real-world implementation of genomic medicine.

总结 多基因风险评分有可能改变常见疾病的管理。然而，关注 存在关于PRS临床实施的问题，包括PRS在非白人中的性能可能降低 人口以及需要为使用 减贫战略在卫生保健决策中的作用。在西北，我们将通过三个主要的科学解决这些问题 与PRS临床使用相关的问题：1）使用PRS是否有助于改善对风险的依从性 管理策略和改善临床结果？2)高风险PRS是否在文化上表现为 敏感和量身定制的风险沟通改善了不同种族和民族的依从性和结果 群组？3)我们能否开发和测试信息技术，将PRS存储在EHR中，并提供临床 决策支持（CDS）来帮助提供者在临床上使用PRS？实现招聘、保留和成果 监测，我们将创建，然后在整个西北传播智能手机应用程序， 电子病历和基因组学（eMERGE）网络，以促进eMERGE的目标 4（e4）。西北大学一直是西北大学研究人员eMERGE所有阶段的主要贡献者 在网络中担任关键领导角色。西北大学以前在电子表型方面的丰富经验 包括使用从我们的企业数据仓库中提取的信息，沿着基因组学， 流行病学专业知识在许多领域，包括PRS基因组发现项目。我们有一个 证明有能力招募和保留大量不同种族的临床人群，以获得遗传结果 返回，并重复成功整合遗传结果到西北大学的电子健康记录， 离散的、可计算的实验室值，从而实现有效的临床决策支持。我们将采用创新 在不同人群中具有更高成功率的招募技术。作为e4的参与者， 我们将实施一项名为ENDORSED（eMERGE Northwestern Develops Optimized）的计划 每个人的DNA的风险分数）。通过以下目标，核可将评估减贫战略的效用， 包括不同的人群。在目标1中，我们将计算并验证所选常见疾病的PRS 特别是因为他们有医学上可行的结果。目标2将招募2500名受试者， 参与eMERGE 4，利用西北医学广泛的临床网络。目标3将 使用行为理论创建文化敏感的沟通工具，然后将PRS数据整合到 电子健康记录目标4将检查减贫战略前后的结果和行为吸收 回报.这些目标的完成将评估和评价减贫战略在不同国家的常见疾病中的使用情况。 产生关于基因组医学实际应用的重要数据的小组。

项目成果

Evaluation of the portability of computable phenotypes with natural language processing in the eMERGE network.

• DOI: 10.1038/s41598-023-27481-y
• 发表时间: 2023-02-03
• 期刊: Scientific reports
• 影响因子: 4.6

Desiderata for the development of next-generation electronic health record phenotype libraries.

为开发下一代电子健康记录表型库的发展。

• DOI: 10.1093/gigascience/giab059
• 发表时间: 2021-09-11
• 期刊: GigaScience
• 影响因子: 9.2
• 作者: Chapman M;Mumtaz S;Rasmussen LV;Karwath A;Gkoutos GV;Gao C;Thayer D;Pacheco JA;Parkinson H;Richesson RL;Jefferson E;Denaxas S;Curcin V
• 通讯作者: Curcin V

Comprehension and personal value of negative non-diagnostic genetic panel testing.

• DOI: 10.1002/jgc4.1327
• 发表时间: 2021-04
• 期刊: Journal of genetic counseling
• 影响因子: 1.9
• 作者: Hoell C;Aufox S;Nashawaty N;Myers MF;Smith ME
• 通讯作者: Smith ME