# Genetic Architecture of Parkinson's Disease in African-American and Latino Veterans

> **NIH VA I01** · VA PUGET SOUND HEALTHCARE SYSTEM · 2024 · —

## Abstract

Parkinson’s disease (PD) is the fastest growing neurological disorder and its worldwide prevalence is expected
to double by the year 2040, a trend that some have labeled the “PD pandemic.” Disease disease-modifying
therapies and better methods of detection in early or pre-symptomatic phases are desperately needed and
data from human genetic studies have moved us much closer to those goals. Unfortunately, such studies have
largely excluded individuals of non-European origin which risks further worsening existing health disparities for
minority populations. The project seeks to address this gap in knowledge by studying the genetic architecture
of PD in African American and Latino participants in the Million Veteran Program (MVP) and other cohorts.
The research team assembled for this project has extensive expertise in clinical movement disorders,
bioinformatics, molecular genetics, and statistical genetics with specialized knowledge in mapping disease
genes in “admixed” (mixed ancestry) populations. This same group of investigators recently published the first
and only admixture mapping analysis and genome-wide association study (GWAS) of PD ever conducted in a
Latino population (based on a cohort from the Latin American Research Consortium on the Genetics of
Parkinson’s Disease [LARGE-PD]).
The fundamental approach will be to perform two complementary techniques (1) admixture mapping, a
technique that leverages local ancestry to identify regions of the genome where ancestry from a particular
ancestral population is inherited more frequently in cases vs controls, and (2) Tractor GWAS, a new analytical
approach that unlike traditional GWAS methods is designed to accommodate admixed individuals. A Discovery
sample will be created using cohorts from MVP and the Veterans Parkinson’s Disease Genetics Initiative (Vet-
PD) and a Replication sample will be assembled from LARGE-PD and several publicly available datasets.
Admixture mapping and Tractor GWAS will first be performed on the Discovery Sample, analyzing each
ancestry group separately and all groups combined. We will also perform the “variant-set test for association
using annotation information” (STAAR) to perform gene-centric association tests of rare variants that are not
suitable for single-marker analyses (such as GWAS). These processes will be repeated in the Replication
sample to validate results. Prioritization of candidate regions discovered will be performed using a combination
of (1) physical position on the genome (positional mapping), (2) expression quantitative trait locus (eQTL)
mapping, and (3) chromatin interaction mapping.
In addition, polygenic risk scores (PRS) will be calculated. A PRS is an estimate of an individual’s genetic
liability to a trait or disease, calculated according to their genotype profile and relevant GWAS data. These
scores have been applied to an increasing number of diseases with the eventual goal of risk stratification
followed by clinical interventions. Bu...

## Key facts

- **NIH application ID:** 10866425
- **Project number:** 5I01BX005978-02
- **Recipient organization:** VA PUGET SOUND HEALTHCARE SYSTEM
- **Principal Investigator:** CYRUS P ZABETIAN
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10866425

## Citation

> US National Institutes of Health, RePORTER application 10866425, Genetic Architecture of Parkinson's Disease in African-American and Latino Veterans (5I01BX005978-02). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10866425. Licensed CC0.

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