PT - JOURNAL ARTICLE AU - Marci L. B. Schwartz AU - Cara Zayac McCormick AU - Amanda L. Lazzeri AU - D’Andra M. Lindbuchler AU - Miranda L. G. Hallquist AU - Kandamurugu Manickam AU - Adam H. Buchanan AU - Alanna Kulchak Rahm AU - Monica A. Giovanni AU - Lauren Frisbie AU - Carroll N. Flansburg AU - F. Daniel Davis AU - Amy C. Sturm AU - Christine Nicastro AU - Matthew S. Lebo AU - Heather Mason-Suares AU - Lisa Marie Mahanta AU - David J. Carey AU - Janet L. Williams AU - Marc S. Williams AU - David H. Ledbetter AU - W. Andrew Faucett AU - Michael F. Murray TI - A Model for Genome-First Care: Returning Secondary Genomic Findings to Participants and Their Healthcare Providers in a Large Research Cohort AID - 10.1101/166975 DP - 2017 Jan 01 TA - bioRxiv PG - 166975 4099 - http://biorxiv.org/content/early/2017/08/03/166975.short 4100 - http://biorxiv.org/content/early/2017/08/03/166975.full AB - Background Research cohorts with linked genomic data exist, or are being developed, at many research centers. Within any such “sequenced cohort” of more than 100 participants, it is likely that there are participants with previously undisclosed risk for life-threatening monogenic diseases that could be identified with targeted analysis of their existing data. Identification of such disease-associated findings are not usually primary to the enrollment research goals. At Geisinger Health System, MyCode® Community Health Initiative (MyCode) participants represent one such large sequenced cohort. Since 2013, MyCode participants in discovery research have been consented for secondary analysis of their existing research genomic sequences to allow delivery of medically actionable findings to them and their healthcare providers. This return of genomic results program was developed to manage an anticipated 3.5% of MyCode participants who will receive clinically confirmed genomic variants from an approved gene list out of more than 150,000 total participants. Risk-associated DNA sequences alone without any clinical parameter, prompt “genome-first” follow-up encounters.Methods This article describes our process for generating clinical grade results from research-based genomic sequencing data, delivering results to patients and their providers, facilitating targeted clinical evaluations of patients and promoting cascade testing of at-risk relatives. We also summarize our early data about the results generated during this process and our ability to contact patients and their providers to disclose the information.Results This process has been used to generate 343 results on 339 patients. 93% of patients with a result have been successfully contacted about their results as evidenced by direct interaction about their result with the research team or a healthcare provider. 222 healthcare providers have been notified of a result on one or more patient through this result delivery process.Conclusions Here we describe the existing GHS model to deliver genomic data into the electronic medical record and the clinical interactions that are prompted and supported. Elements of this genome-first care model can be applied in other healthcare settings and in national efforts, such as “All of Us”, that wish to establish programs for returning genomic results to research participants.GHSGeisinger Health SystemMyCodeMyCode Community Health InitiativeACMGAmerican College of Medical Genetics and GenomicsCLIAClinical Laboratory Improvement AmendmentEHRElectronic Health RecordG76Geisinger 76 Gene ListVUSVariant of Uncertain SignificanceVCFVariant Call FileLMMPartners Healthcare’s Laboratory for Molecular MedicinePCPPrimary Care ProviderLHSLearning Healthcare SystemWESWhole Exome Sequencing,P/LPPathogenic/likely pathogenic