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.

概括 多基因风险评分有可能改变常见疾病的管理。但是，担心 存在于PRS的临床实施，包括非白人中PR的可能性降低的可能性 人群以及建立改善的沟通和扩展信息的需求支持使用 医疗保健决策中的公关。在西北地区，我们将通过三个主要科学解决这些问题 与PR的临床使用有关的问题：1）PRS的使用确实有助于改善依从性风险 管理策略并改善临床结果？ 2）在文化上表现出高风险PR 敏感和量身定制的风险交流改善了潜水员种族和种族的依从性和结果 小组？ 3）我们可以开发和测试将PR存储在EHR中并提供临床的信息技术 决策支持（CD）在临床上使用PRS使用的提供者？能够招募，保留和结果 监视，我们将创建并在西北航空上传播智能手机应用程序，并 可能的是电子病历和基因组学（Emerge）网络，以促进出现的目标 4（E4）。西北航空一直是西北调查人员出现的所有阶段的主要贡献者 在网络中担任关键领导角色。西北地区以前在电子表型方面的丰富经验 涉及使用从我们的企业数据仓库中提取的信息以及基因组学和 基因组发现项目在内的许多领域（包括PRS）的流行病学专业知识。我们有一个 表现出招募和保留大量和种族多样化的临床人群的能力，以获得遗传结果 返回，并重复将遗传结果成功整合到西北的电子健康记录中 离散的，可计算的实验值可实现有效的临床决策支持。我们将采用创新 在潜水员人群中取得成功率较高的入学技术。作为E4的参与者 财团我们将实施一个名为认可的计划（Emerge Northwestern开发优化 每个人的DNA的风险得分）。通过以下目的，认可将评估PRS的效用， 包括潜水员人群。在AIM 1中，我们将计算并验证选定常见疾病的PR AIM 2将招募2500名受试者 利用西北医学广泛的临床网络，参与Emerge 4。目标3意志 使用行为理论来创建具有文化敏感的交流工具，然后将PRS数据集成到 电子健康记录。 AIM 4然后将检查PR之前和之后的结果和行为的吸收 返回。这些目标的完成将评估和评估潜水员常见疾病的PR使用 产生有关基因组医学实施的重要数据的小组。

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.

• 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