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

摘要 在美国，60%的成年人患有一种慢性病，40%的人患有两种或两种以上的慢性病。统称 疾病是导致死亡和残疾的主要原因，占我们国家3.3万亿美元的90%以上 每年的医疗费用。 全基因组关联研究（GWAS）已经确定了疾病的遗传基础， 多基因风险评分（PRS）的发展，可能有助于预测的发生和进展， 常见病 与eMERGE团队合作，我们将选择15种影响公共卫生的疾病。对于这些疾病， 我们将最终确定将采用的生产者责任计划，包括为少数民族群体进行的调整（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GRE阈值，在该阈值下， 建议（RRR）与实践指南一致。加强种族特异性评价 PRS，我们带来了额外的30,0000名AA。 我们将进行一项试点伦理法律的社会影响研究，以探讨患者对使用FHX的看法， 用于估计亚拉巴马基因组健康倡议（全州队列）参与者疾病风险的PRS。 研究结果将为知情同意、教育材料和沟通战略的制定提供信息， 加强eMERGE参与者的招聘和保留。 我们将前瞻性招募2,500名患者，其中>75%的患者来自医疗服务不足的社区， 结合PRS、FHX和临床数据，计算所有患者选定的15种疾病的GRE。为 GRE超过预先规定阈值的高风险患者（在整个研究中招募的20，000例患者中，n约为5000例） 网络），部署临床决策支持（CDS）并呈现GRA和RRR。我们预计≥50%的吸收率 RRRs。 我们将评估GRA-RRR的采用是否会改善结果。我们将评估三个结果：吸收 GRA-RRR（实施结果）、坚持门诊访视（参与结果）以及 疾病/控制（临床结果;例如血糖、胆固醇）。 虽然研究已经确定了常见疾病的基因组特征，但基因组风险评估， 在临床护理中尚未实施识别并在适当情况下对高危患者进行预治疗。这是至关重要的 这是利用基因组学预防疾病的第一步。我们将专业知识和经验 与eMERGE调查团队合作，迈出这至关重要的第一步。

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.