# EHR-based Genomic Discovery and Implementation

> **NIH NIH U01** · MAYO CLINIC ROCHESTER · 2020 · $1,085,761

## Abstract

PROJECT SUMMARY
In this application we propose to build on our work in the previous three phases of eMERGE to develop and
validate polygenic risk scores (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 and controls for the 15 diseases and ascertain clinical risk
scores for each disease by extracting relevant variables from the electronic health record (EHR). Next, using
existing eMERGE genotype and phenotype data (n=105,000) and publicly available (TopMed, AoU, MVP,
UKBB) datasets, we will calculate candidate loci or genome wide PRS using 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. We have previously applied such methodology for coronary 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 (1800 adults and 200 adolescents) and
Phoenix AZ (500 adults of Hispanic ethnicity). 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 clinical decision support (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, risk reduction measures, and changes in modifiable risk factors. In
addition we will examine the economic, behavioral and psychosocial implications of returning PRS. Our focus
on PRS brings genomic medicine to the population and 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 105,000 eMERGE participants as well as other publicly available datasets to
validate PRS for 15 common diseases; 2) Deploy novel methods for integrating PRS in the EHR with linkage to
CDS that incorporates guideline based clinical recommendations and develop scalable methods for disclosing
PRS results to participants; 3) Enroll 2500 persons to undergo CLIA genotyping using dense SNP arrays and
return comprehensive risk profiles that include PRS; 4) Assess clinical, cost/utilization and psychosocial
outcomes following return of results.

## Key facts

- **NIH application ID:** 9989313
- **Project number:** 2U01HG006379-09
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Iftikhar J Kullo
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,085,761
- **Award type:** 2
- **Project period:** 2011-08-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989313

## Citation

> US National Institutes of Health, RePORTER application 9989313, EHR-based Genomic Discovery and Implementation (2U01HG006379-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9989313. Licensed CC0.

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