Genomic Medicine at Northwestern: Discovery and Implementation

 描述(由申请人提供)：国家人类基因组研究所对基因组医学的愿景包括发现和实施两个要素。这一愿景旨在通过将基因组信息适当地整合到临床护理中来改进医学实践，同时继续更好地了解基因组变异的基本原理、基因组结构以及遗传变异在疾病和治疗结果中的作用。Emerge网络为发现做出了关键贡献，它利用临床护理过程中电子健康记录(EHR)中捕获的信息开发了高通量电子表型分析方法，并通过全基因组关联研究确定了疾病和数量性状与常见遗传变异之间的新关联。Emerge还通过开发与EHR的接口、临床决策支持、保存基因组变异信息和将临床相关变异转移到EHR中的策略，以及向医生和患者返回基因组变异信息，为疾病易感性和改善治疗管理，特别是处方和药物剂量方面的改善，在实施基因组医学方面发挥了领导作用。此外，制定和传播执行最佳做法一直是Emerge的一个重要目标。作为Emerge I和Emerge II的参与者，西北大学(NU)通过其与EHR相连的生物库Nugene，为所有这些活动做出了重大贡献，几名NU调查人员发挥了关键的领导作用。在这项应用中，我们建议利用NU的基础设施和专业知识来(A)从来自EHR数据挖掘的表型中发现至少100个测序基因中的罕见变异和Emerge Gwas数据集中的常见变异之间的关联，(B)招募2000名同意接受基因组信息并允许将信息存储在他们的EHR中的患者参与研究，(C)将临床可操作的结果返回给医疗保健提供者和患者，以确定效用和临床结果，以及(D)开发和分享与返回基因组结果相关的最佳实践，教育医生和患者，以及相关的伦理、法律和社会影响。 成功实现这些目标将提供新的科学知识和重要的现实世界经验，将推动NHGRI在其战略愿景的各个领域的发现和实施。

 DESCRIPTION (provided by applicant): National Human Genome Research Institute's vision for genomic medicine includes elements of both discovery and implementation. This vision seeks to improve the practice of medicine through the appropriate integration of genomic information into clinical care while continuing to better understand fundamentals of genomic variation, genome structure and the role of genetic variation in disease and therapeutic outcomes. The eMERGE network has made critical contributions to discovery by developing methods for high throughput electronic phenotyping using information captured in electronic health records (EHRs) in the course of clinical care and identifying new associations between diseases and quantitative traits with common genetic variants through genome wide associations studies. eMERGE has also provided leadership in implementing genomic medicine by developing interfaces with EHR, clinical decision support, strategies for holding genomic variant information and transferring clinically relevant variants into the EHR, and returning genomic variant information to physicians and patients, both for disease susceptibility and for improving therapeutic management, particularly with prescription and dosing of medications. In addition, development and dissemination of best practices for implementation has been an important goal of eMERGE. As a participant in both eMERGE I and II, Northwestern (NU) through its EHR-linked biobank NUgene, has made significant contributions to all of these activities, with several NU investigators playing key leadership roles. In this application we propose to leverage the infrastructure and expertise at NU to (a) discover associations between rare variants in at least 100 sequenced genes and common variants from the eMERGE GWAS dataset from phenotypes derived from EHR data mining, (b) enroll 2000 patients into the study who agree to receive genomic information and allow the information to be stored in their EHR, (c) return clinically actionable results to healthcare providers and patients to determine utility and clinical outcomes, and (d) develop and share best practices related to returning genomic results, educating physicians and patients, and the related ethical, legal and social implications. Successfully achieving these goals will provide new scientific knowledge and significant real world experience that will advance the NHGRI vision for both discovery and implementation across the spectrum of its strategic vision.