EMR-Linked Biobank for Translational Genomics

 描述(申请人提供)：由基因组信息提供的医疗保健开始进入临床实践。电子医疗记录和基因组学(Emerge)网络通过其初始阶段为这一转变提供了许多基础。盖辛格健康系统项目“用于翻译基因组学的EMR链接生物库”旨在以Emerge第二阶段的知识和经验为基础，加快发现和实施，同时扩大我们对基因组学在医学中的社会文化影响的理解。我们将通过三个具体目标来实现这一目标：1)使用现有的生物样品、基因和序列数据以及EMR产生的表型来发现拟议的疾病：家族性高胆固醇血症和慢性鼻窦炎；2)开发和测试在临床实践中实现基因组信息的方法；3)探索、开发和实施围绕临床相关基因组结果的以家庭为中心的沟通的新方法。我们目前有超过6万名患者广泛同意进行研究，其中同意返回结果和在电子健康记录中沉积的比例很大，而且还在不断增加。超过18,000名患者在高密度平台上进行了基因分型。我们建议的两种表型，家族性高胆固醇血症(FH)和慢性鼻-鼻窦炎(CRS)之所以被选中，是因为这两种疾病在美国都有重大的公共健康影响，但它们也非常适合该项目的特定目标。它们为创新和推广现有的Emerge方法提供了机会。虽然这些创新中的许多将利用作为项目一部分进行的排序，但在资助机会中强调的其他几个领域将扩大Emerge研究的范围。Emerge III的重点领域之一是探索可操作结果的家庭回报。FH非常适合这一点，因为目前的临床建议是对所有确诊患者的家庭成员进行级联测试。目前，这依赖于患者联系有风险的家庭成员，但这并不是最理想的。我们将使用定性和定量的方法来探讨这一问题，并利用结果来设计和测试新颖的家庭沟通策略。基因-环境相互作用在疾病的发展和严重程度中起着重要作用。这些都很难研究。我们提出了新的方法，利用盖辛格健康系统和Emerge Network的资产来开发和应用方法，以扩展研究环境对CRS影响的现有项目。这将包括第一次大规模的全环境关联研究(EWAS)。最后，我们建议带头努力将经济建模和分析的工具应用于Emerge项目，以开始量化基因组医学在美国医疗体系中实施的价值。这些拟议的创新将放大Emerge计划在将基因组医学从梦想变成现实方面已经产生的重大影响。

 DESCRIPTION (provided by applicant): Medical care informed by genomic information is beginning to move into clinical practice. The Electronic Medical Records and Genomics (eMERGE) network through its initial phases has provided much of the groundwork for this transformation. The Geisinger Health System project, "EMR-Linked Biobank for Translational Genomics" intends to build on the knowledge and experience from eMERGE phase II to accelerate discovery and implementation while expanding our understanding of the sociocultural implications of genomics in medicine. We will accomplish this goal through three specific aims: 1) Use existing biospecimens, genotype and sequence data and EMR-generated phenotypes for discovery in the proposed disorders: familial hypercholesterolemia and chronic rhinosinusitis, 2) Develop and test approaches for implementation of genomic information in clinical practice, 3) Explore, develop and implement novel approaches for family-centered communication around clinically relevant genomic results. We currently have over 60,000 patients broadly consented for research with a large and increasing proportion consented for return of results and deposition in the electronic health record. Over 18,000 patients are genotyped on high density platforms. Our two proposed phenotypes, familial hypercholesterolemia (FH) and chronic rhinosinusitis (CRS) were chosen because both conditions have a significant public health impact in the United States, but they are also ideally suited to the specific aims of the project. They provide opportunities for innovation and extension of current eMERGE methods. While many of these innovations will take advantage of the sequencing done as part of the project, there are several other areas emphasized in the funding opportunity that will broaden the scope of eMERGE research. One of the areas of emphasis for eMERGE III is exploring the familial return of actionable results. FH is well suited to this, as the current clinical recommendation is cascade testing of family members for all diagnosed patients. Currently this relies on the patient to contact at risk family members, but this is less than optimal. We will explore this issue using qualitative and quantitative methods and use the results to design and test novel family communication strategies. Gene-environment interactions play an important role in the development and severity of disease. These are very difficult to study. We propose novel approaches that leverage the assets of Geisinger Health System and the eMERGE Network to develop and apply methods to extend existing projects that study the impact of environment on CRS. This would include the first large scale environment-wide association studies (EWAS). Finally, we propose to lead efforts to apply the tools of economic modeling and analysis to eMERGE projects to begin to quantify the value of implementation of genomic medicine in the US healthcare system. These proposed innovations will magnify the already significant impact that the eMERGE program has had in moving genomic medicine from a dream to a reality.