# Polygenic risk scores and health disparities: the role of blood cells immune response and evolutionary adaptation

> **NIH NIH U01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $991,906

## Abstract

Abstract
The large number of disease susceptibility loci identified from genome-wide association studies (GWAS) is
enabling polygenic risk scores (PRS) to deliver on their promise to improve health outcomes and to transform
the practice of personalized medicine. The reduced quality of PRS for common diseases and related
quantitative traits for populations of recent African, Asian, and Native American ancestries relative to those for
populations of recent European ancestries, however, threatens to create a new class of disparities in the
delivery of healthcare based on PRS. The number of individuals of non-European ancestry with genome
interrogation are growing much more rapidly now than 5 years ago; nevertheless, the number of individuals of
recent European ancestries with genome interrogation grows still more rapidly and it is likely to be many years
before sample sizes for genome interrogation in even major continental groups are close to proportional to
relative population sizes. Thus, it is critical to optimize PRS performance for diverse populations in as
many ways as we can. Given the substantial and growing fraction of the US population with genomes
admixed from different continental ancestries, we believe that high quality PRS for much of the US population
is unlikely to be achieved without properly accounting for local ancestries. Similarly, focused strategies to
identify high-impact but population-specific variants could improve the quality of PRS in populations with such
alleles. DNA variants from regions with a signature of natural selection often demonstrate such properties, and
have been shown to be enriched among top associations for a number of hematological and
immune/inflammatory traits that are important biomarkers for key chronic diseases. We propose to focus our
PRS studies on hematological and immune/inflammatory traits and their associated chronic diseases and to
extend methods for the development of PRS to accommodate estimates of local ancestry, high impact
population-specific variants and multiple endophenotypes. Thus, our Specific Aims are: 1) Assemble and
harmonize data sets needed to accomplish the goals of the project, including hematological traits (red
blood cell, white blood cell, platelet), and immune/inflammatory traits (CRP, fibrinogen, D-dimer) from: Jackson
Heart Study, Women’s Health Initiative, BioVU, and GeneSTAR. 2) Extend PRS methods to: a) explicitly
model local ancestry; b) accommodate large-effect but population-specific risk alleles (such as those
from regions with a signature of natural selection); and c) enable joint modeling of multiple
endophenotypes; and 3) Develop and apply novel PRS and overall disease prediction models to: a)
estimate risk of common diseases and related biomarkers affected by hematological, thrombotic and
immune/inflammatory biology; and b) enable calculation of PRS-adjusted clinical laboratory values to
reduce structural health disparities.

## Key facts

- **NIH application ID:** 10424445
- **Project number:** 5U01HG011720-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Nancy J Cox
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $991,906
- **Award type:** 5
- **Project period:** 2021-06-08 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10424445

## Citation

> US National Institutes of Health, RePORTER application 10424445, Polygenic risk scores and health disparities: the role of blood cells immune response and evolutionary adaptation (5U01HG011720-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10424445. Licensed CC0.

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