# Polygenic Risk of Disease in Populations of Diverse Ancestry

> **NIH NIH U01** · MAYO CLINIC ROCHESTER · 2024 · $592,026

## Abstract

PROJECT SUMMARY
In this application we propose to build on our prior work on polygenic risk scores (PRSs) to extend these to
diverse ancestry groups. By improving risk stratification, PRSs for common diseases have the potential to
transform clinical practice. However, such PRSs must be available for diverse ancestry groups to ensure
equitable implementation of genomic medicine and reduce the potential exacerbation of health disparities in
the context of genomic medicine. Our application aims to address the critical need to develop PRSs for diverse
ancestry groups and will focus on coronary heart disease (CHD) and its risk factors: hypertension, diabetes,
obesity and hypercholesterolemia, collectively an enormous health burden world-wide. CHD is the prototypical
complex disease for the use of PRSs given available validated risk prediction equations that bin individuals into
risk categories and substantial reclassification across these categories by a PRS with consequent therapeutic
implications. As part of the PRS Diversity Consortium (PRS-DC), we will develop methods to generate PRSs
for populations of diverse ancestry using existing and new datasets with genomic and phenotype data for CHD
and its risk factors. We will harmonize data elements across these data sets. The methods we develop will be
applicable towards the generation of PRSs for a broad range of common diseases across diverse populations.
The investigative team is part of the Mayo eMERGE IV application and will serve as a bridge between the
PRS-DC and eMERGE. To generate PRSs for diverse ancestries, we will use data from the eMERGE
consortium, Million Veteran’s Program (MVP), the All of US (AoU) program, dbGAP, PRS-DC sites, UK
Biobank, and collaborations with several international groups representing the Middle Eastern, South Asian
and East Asian cohorts. Our application includes several innovations to enable the use of PRSs for risk
stratification and prevention of CHD in individuals belonging to diverse ancestries. Our specific aims are:
Specific aim 1. Integrate and harmonize phenotype data from heterogeneous sources to enable cross platform
phenotyping and generation of PRSs for common diseases in diverse ancestry groups. Specific aim 2. Develop
PRSs for CHD and its major risk factors (hypertension, diabetes, obesity, hypercholesterolemia) in populations
of diverse ancestry. Specific aim 3. Develop novel statistical and computational methods to account for
diverse genetic ancestry and admixture in models of polygenic risk. Specific aim 4. Develop ‘clinic ready’ PRSs
for diverse ancestry groups by creating reference distributions of a PRSCHD and integrate it with clinical
information to compute absolute risk estimates.

## Key facts

- **NIH application ID:** 10894636
- **Project number:** 5U01HG011710-04
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Daniel J. Schaid
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $592,026
- **Award type:** 5
- **Project period:** 2021-09-08 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894636

## Citation

> US National Institutes of Health, RePORTER application 10894636, Polygenic Risk of Disease in Populations of Diverse Ancestry (5U01HG011710-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10894636. Licensed CC0.

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