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.