EHR-based Genomic Discovery and Implementation

Project: Research project

Project Details


EHR-based Genomic Discovery and Implementation EHR-based Genomic Discovery and Implementation In this application we propose to build on our prior work in the previous three phases of eMERGE related to genomic discovery and return of results to develop and validate PRS for 15 common diseases and combine these with clinical risk scores and family history to create comprehensive risk profiles for 2500 individuals (35% non-European ancestry). We will develop phenotyping algorithms to identify cases, controls for 15 common diseases and ascertain clinical risk scores for each disease by extracting relevant variables from the EHR. Next, using existing eMERGE genotype and phenotype data (n=105,000) and additional cohorts such TopMed, AoU and MVP we will calculate candidate loci or genome wide PRS as previously described incorporating novel methods to adapt these to specific racial/ethnic groups. Validated PRS will be combined with family history and clinical risk scores to create comprehensive risk profiles for participants. We have previously applied such methodology for CHD or heart disease positioning us well to expand this to 14 additional common diseases. To assess the utility of PRS in a prospective cohort, we will recruit participants from Rochester MN (n=1700 EA, 375 non-EA) and Phoenix AZ (n=500 non-EA). DNA will be sent for CLIA-certified genomic testing and we will calculate race/ethnicity specific PRS. Individualized risk estimates will be reported to participants and providers and placed in the EHR with linkage to CDS that includes guideline-based risk-management information. For participants who are at significantly higher risk for developing at least 1 of the 15 diseases (estimated 25% of the cohort), results will be disclosed in-person followed by assessment of outcomes including new tests ordered, surveillance initiated, modifications of therapy, and changes in modifiable risk factors (eg LDL-C in persons at risk for CHD). In addition we will examine the economic, behavioral and psychosocial implications of returning PRS. Our focus on PRS brings genomic medicine to the population. We will continue our partnership with Mountain Park Health Center, a FQHC serving low-income, minority communities across Phoenix AZ, to address concerns about health disparities in the context of genomic medicine. Our specific aims include: 1) Utilize extant genotype and EHR data on 100,000 eMERGE participants as well as other publicly available datasets to validate PRS for 15 common diseases; 2) Deploy SMART on FHIR for integrating PRS in the EHR with linkage to CDS that incorporates guideline based clinical recommendations and develop scalable methods for disclosing genomic risk results to participants; 3) Enroll 2500 persons to undergo CLIA genotyping using dense SNP arrays and return PRS; 4) Assess clinical, cost/utilization and psychosocial outcomes following RoR.
Effective start/end date7/1/204/30/25


  • HHS: National Institutes of Health (NIH): $197,944.00


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