# eMERGE Phase IV Clinical Center at Partners HealthCare

> **NIH NIH U01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $1,216,161

## Abstract

Abstract: To enable the application of PRS development and implementation, our eMERGE IV proposal from
Partners HealthCare leverages a large biobank (>105,000 consented with genotype data on 40,000), clinical
data in the electronic health records (EHR) for >4 million patients from the largest integrated health care
provider in New England, advanced bioinformatics expertise, prior leadership in PRS development and state-
of-the-art genetic analysis, established expertise in returning genomics results, and experience using
information technology to transform clinical processes and assessing outcomes. We propose to build on our
expertise to accomplish the specific aims: Aim 1 (Discovery): Hypothesis: Polygenic risks scores will
allow us to stratify eMERGE subjects based on genetic risk for common complex traits. Using the
largest available genomic data resources, we will calculate and validate new PRS for coronary artery disease,
atrial fibrillation, type 2 diabetes, colorectal cancer and major depression across diverse ancestries. We will 1)
compare and benchmark the performance of existing PRS construction methods in different ancestral groups,
2) develop novel statistical methods for robust trans-ethnic PRS prediction, and integrate PRS with established
clinical risk factors and family history. We will obtain PRS from our network colleagues for an additional 15-e-
phenotypes (total 20) with a goal of identifying high-risk individuals, e.g., top 2% of PRS risk Aim 2
(RiskInsight Report/ELSI): We will develop a “Risk Insight Report” with clinical risk factors, family
history, and PRS with evidence-based recommendations for high risk participants (top 2% of
phenotype specific PRS distribution) for electronic clinical implementation. We will assess risk
communication formats in our ELSI Sub-Aim 1: To test the impact and interpretability of two mock
RiskInsight Reports summarizing PRS as either (a) dichotomous (defining the patient as high-risk vs
intermediate/low risk) or (b) quantitative (providing a numerical estimate of the percentile of risk for the patient),
with linked clinical recommendations in both cases. We will then assess, through surveys of diverse HCPs and
patients, the extent to which the mock reports are understood by both HCPs and patients. Aim 3 (Outcomes):
Hypothesis: Physicians will alter their surveillance and treatment of patients based on eCDS of
RiskInsight Reports. Among HCPs for high-risk subjects, we will see at least one change in clinical
care after disclosure discussions with subjects. We will recruit 2500 participants for implementation of
clinical PRS in RiskInsight Reports using a SMART on FHIR app for eCDS integrated with the EHR. The
primary outcome will be whether any HCP took any action within 12 months after receipt of e-CDS defined by
ordering screening tests, prescribing a preventive medication, or providing lifestyle advice. We will conduct
analyses of the effect of disclosing results to high risk participants...

## Key facts

- **NIH application ID:** 9988785
- **Project number:** 2U01HG008685-05
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** ELIZABETH W KARLSON
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,216,161
- **Award type:** 2
- **Project period:** 2015-09-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988785

## Citation

> US National Institutes of Health, RePORTER application 9988785, eMERGE Phase IV Clinical Center at Partners HealthCare (2U01HG008685-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9988785. Licensed CC0.

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