Integrating Genomic Risk Assessment for Chronic Disease Management in a Diverse Population

整合基因组风险评估以进行不同人群的慢性病管理

• 批准号: 10852376
• 负责人: JAMES J CIMINO
• 金额: $ 34万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-14 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10852376
• 关键词: Accounting; Adherence; Adopted; Adult; African American; African ancestry; Alabama; American; Asian; Blood Glucose; Body mass index; Cause of Death; Cessation of life; Cholesterol; Chronic Disease; Clinic Visits; Clinical; Clinical Data; Clinical Trials; Collaborations; Communication; Complex; Consent; Data; Development; Diabetes Mellitus; Disease; Disease Management; Education; Educational Materials; Environment; European; Evaluation; Family; Family history of; Genes; Genetic; Genomics; Genotype; Health; Health Care Costs; Heart Diseases; Hispanic; Individual; Informatics; Life Style; Link; Malignant Neoplasms; Medical; Methodology; Methods; Minority Health Research; Modification; Morbidity - disease rate; Outcome; Participant; Patients; Phenotype; Population; Population Heterogeneity; Practice Guidelines; Prevalence; Public Health; Publications; Race; Recommendation; Recording of previous events; Reporting; Research; Research Design; Risk; Risk Assessment; Risk Estimate; Risk Management; Risk Reduction; Sample Size; Sampling; Specific qualifier value; Trust; Underrepresented Minority; United States; biobank; clinical care; clinical decision support; cohort; digital; disability; disorder risk; ethical, legal, and social implication; experience; gene interaction; genetic architecture; genome wide association study; genomic signature; health disparity; health record; high risk; implementation outcomes; improved outcome; indexing; medically underserved; medically underserved population; mortality; phenotypic data; phenotyping algorithm; polygenic risk score; prevent; prospective; racial minority; racial minority population; racial population; recruit; statistics; tool; underserved community; uptake; visit adherence

Abstract In the United States, 60% of adults have a chronic disease and 40% have two or more. Collectively these diseases are the leading causes of death and disability accounting for >90% of our nation’s $3.3 trillion annual health care costs. Genome-wide association studies (GWAS) have identified genetic underpiinings of disease and enabled the development of polygenic risk scores (PRS) that may help to predict the occurrence and progression of common dieases. Working with the eMERGE team, we will select the fifteen diseases of public health impact. For these diseases, we will finalize the PRS to be adopted including adaptations (if any) for minority race groups, the genotyping array, the family history (FHx) tool and key clinical variables to be used in calculating genomic risk estimates (GRE). We will identify GRE thresholds at which genomic risk assessment (GRA) with risk reduction recommendations (RRR) in concordance with practice guidelines. To strengthen the evaluation of race-specific PRS, we bring an additional cohort of 30,0000 AAs. We will conduct a pilot ethical legal social implications study, to explore patient perspectives on use of FHx and PRS for estimating disease risk among Alabama Genomic Health Initiative (a state wide cohort) participants. The results will inform the development of consent, educational materials and a communication strategy to enhance recruitment and retention of eMERGE participants. We will prospectively recruit 2,500 patients with >75% patients from medically underserved communities, incorporate PRS, FHX and clinical data to compute GRE for the selected fifteen diseases for all patients. For high-risk patients, where GRE exceeds pre-specified thresholds (n~ 5000 of the 20,000 recruited across the network), deploy clinical decision support (CDS) and present the GRA and RRR. We expect ≥50% uptake of RRRs. We will assess whether the uptake of GRA-RRR improve outcomes. We will assess three outcomes: uptake of GRA-RRR (implementation outcome), adherence to clinic visits (engagement outcome), and surrogates of disease / control (clinical outcome; e.g. blood sugar, cholesterol). Although research has identified genomic signatures of common diseases, genomic risk assessments to identify, and if appropriate, pre-treat at-risk patients have not been implemented in clinical care. This is the vital first step to leverage the power of genomics to prevent disease. We bring our expertise and experience to collaborate with the eMERGE investigative team to take this vital first step.

摘要 在美国，60%的成年人患有慢性病，40%患有两种或两种以上的慢性病。总的来说，这些 疾病是导致死亡和残疾的主要原因，占我国3.3万亿美元人口的90% 每年的医疗保健费用。 全基因组关联研究已经确定了疾病的遗传基础，并使 多基因风险评分(PR)的发展可能有助于预测糖尿病的发生和发展 常见病。 我们将与Emerge团队合作，选出影响公共卫生的15种疾病。对于这些疾病， 我们将最终确定将采用的方案，包括少数族裔群体的改编(如果有的话)、基因分型 阵列、家族史(FHx)工具和用于计算基因组风险估计的关键临床变量 (GRE)。我们将确定基因组风险评估(GRA)可降低风险的GRE阈值 与实践指南一致的建议(RRR)。加强对特定种族的评估 PRS，我们带来了额外的300,000名AA。 我们将进行一项伦理法律社会影响的试点研究，以探索患者对FHx和FHx使用的看法 用于评估阿拉巴马州基因组健康倡议(全州范围的队列)参与者的疾病风险的PR。 结果将指导制定同意、教育材料和沟通战略，以 加强对Emerge参与者的招聘和留住。 我们将前瞻性地招募2500名患者，其中75%的患者来自医疗服务不足的社区， 综合PRS、FHX和临床资料，计算所有患者所选15种疾病的GRE。为 高危患者，GRE超过预先指定的阈值(在全国范围内招募的20,000名患者中有5,000名 网络)，部署临床决策支持(CDS)，并提供GRA和RRR。我们预计≥将采用50%的 RRRS。 我们将评估GRA-RRR的摄取是否会改善结果。我们将评估三个结果： GRA-RRR(执行结果)、坚持诊所就诊(接洽结果)和 疾病/控制(临床结果；例如血糖、胆固醇)。 尽管研究已经确定了常见疾病的基因组签名，但基因组风险评估 识别并在适当的情况下对高危患者进行预治疗尚未在临床护理中实施。这是至关重要的 利用基因组学的力量预防疾病的第一步。我们将我们的专业知识和经验带到 与Emerge调查团队合作，迈出这至关重要的第一步。

项目成果

Key Contextual Factors Involved with Participation in Medical and Genomic Screening and Research for African American and Caucasian Americans: A Qualitative Inquiry American Journal of Community Genetics.

非裔美国人和白人美国人参与医学和基因组筛查和研究的关键背景因素：定性调查美国社区遗传学杂志。

• DOI: 10.21203/rs.3.rs-4132207/v1
• 发表时间: 2024
• 期刊: Research square
• 作者: Smith,CrystalLederhos;Stark,BConnor;Kobalter,McKenna;Barks,MaryCarol;Nakano-Okuno,Mariko;Romesburg,EllenWeger;Limdi,Nita;May,Thomas
• 通讯作者: May,Thomas