# Rational Integration of Polygenic Risk Scores (RIPS)

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $999,221

## Abstract

Project Summary
 There has been extraordinary growth in new techniques to predict common, complex disease
based on polygenic risk scores (PRS). Without an understanding grounded in evidence, it is
unlikely that the clinical use of PRS will propagate from highly specialized applications and
environments to become adopted more broadly and provide greater benefit to the US
population. Critical challenges include: 1) understanding the impact of clinical PRS for multiple
diseases on long-term patient outcomes, 2) identifying risk thresholds for return of results that
optimize patient outcomes and provide cost-effective care, 3) understanding how PRS
performance across diverse populations may affect existing disparities and subsequent patient
outcomes. We propose to address these challenges using decision analytic modeling and by
building on our extensive work in this area to create a novel framework capable of assessing
PRSs in the context of monogenic and clinical risks. We have already created clinical-economic
models to project lifetime clinical impact and cost-effectiveness for population-level genomic
screening with return of monogenic disease risks associated with three CDC Tier 1 conditions:
hereditary breast and ovarian cancer, Lynch syndrome, and familial hyperlipidemia. As part of
this proposal, titled Rational Integration of Polygenic Risk Scores (RIPS), we will create models
to assess the clinical outcomes and economic value of population screening using PRS in real-
world settings and applied to large and diverse populations. The Aims of the proposal include
1) to evaluate published and real-world evidence on the clinical value of adding PRS to inform
comprehensive genomic risk assessment; 2) to understand the impact of PRS performance
and return risk thresholds on incremental clinical benefit and cost effectiveness for breast
cancer, atherosclerotic cardiovascular disease, and colorectal cancer, and 3) to develop
research priorities for the equitable development and implementation of PRS across
underserved and underrepresented populations.

## Key facts

- **NIH application ID:** 10366293
- **Project number:** 1R01HG012262-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Jing Hao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $999,221
- **Award type:** 1
- **Project period:** 2022-03-10 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10366293

## Citation

> US National Institutes of Health, RePORTER application 10366293, Rational Integration of Polygenic Risk Scores (RIPS) (1R01HG012262-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10366293. Licensed CC0.

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