# Polygenic Risk Scores for Diverse Populations - Bridging Research and Clinical Care

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2022 · $132,000

## Abstract

ABSTRACT
This supplement will expand on the currently funded grant R01 HL151152 entitled “Polygenic Risk Scores
(PRS) for Diverse Populations - Bridging Research and Clinical Care” through a focused polygenic risk scores
analysis of hypertension (HTN) and related traits, an incorporation of All of Us diverse data, and incorporation
of lifestyle effects, which were not prioritized in the original R01 application. Cardiovascular disease (CVD) and
its risk factors impose major societal burdens and are leading causes of morbidity, mortality, and disability.
Recent reports documenting a slowing or reversal of four decades of declining CVD mortality rates motivate an
innovative transformation of CVD prevention, diagnosis, and treatment. Genomic research, a cornerstone of
precision medicine, offers such a transformation through the application of PRS, the aggregation of risk variants
into a single score. However, the vast majority of participants included in the PRS research to-date have been
of European ancestry (EA). We have demonstrated that EA-derived PRS are not generalizable to racially and
ethnically diverse populations, as EA-derived PRS predict CVD and CVD risk factors with much greater
accuracy in EA than in all other race and ethnicity groups. This lack of generalizability reflects differential
prediction accuracy and unpredictable bias in the context of population structure that characterizes racially and
ethnically diverse populations. Despite these limitations, efforts to commercialize and provide to patients EA-
derived PRS are underway, even though the application of EA-derived PRS to diverse populations has the
strong potential to exacerbate longstanding racial and ethnic disparities in CVD and CVD risk factors. Research
that enables estimation, validation, calibration, and contextualization of PRS in racially and ethnically diverse
populations is needed to ensure that all populations reap the benefits of precision medicine. We will utilize data
from the Population and Architecture using Genetics and Epidemiology (PAGE) study and aim to fully integrate
the All of Us Research Program for independent validation. We propose (i) the creation of unbiased PRS for
HTN-related traits (systolic and diastolic blood pressure and HTN) in the ancestrally diverse PAGE study
population. The PRS will be validated in the All of Us Research Program; (ii) Contextualization/Performance
across key lifestyle factors: Develop and evaluate a lifestyle risk score (LRS) composed of non-genetic clinical
and prognostic data to improve predictive performance of PRS. The PRS+LRS will be validated in the All of Us
Research Program; and (iii) Clinical Characterization: Evaluate the clinical significance of HTN-related PRS to
improve biologic insight of HTN-related diseases using the All of Us research program to prioritize functional
follow-up on genes and pathways with greatest clinical impact. We will conduct phenome-wide association
(PheWAS) analyses to validate ex...

## Key facts

- **NIH application ID:** 10658157
- **Project number:** 3R01HL151152-04S1
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Christopher R Gignoux
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $132,000
- **Award type:** 3
- **Project period:** 2020-08-20 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10658157

## Citation

> US National Institutes of Health, RePORTER application 10658157, Polygenic Risk Scores for Diverse Populations - Bridging Research and Clinical Care (3R01HL151152-04S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10658157. Licensed CC0.

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