# Identifying novel Parkinson'’s disease genes exploring understudied Latino populations

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2024 · $589,629

## Abstract

Human genetic studies have greatly accelerated progress in understanding the etiopathogenesis of
Parkinson's disease (PD). To date, six causal genes (SNCA, PARK2, PINK1, DJ-1, LRRK2, and VPS35) and
ninety susceptibility genes/loci (e.g., MAPT, GBA) have been identified for PD, mostly in populations of
European or Asian ancestry. However, these genes explain only a small proportion of PD heritability. Thus,
additional novel genes await discovery, and we believe that the highest likelihood of success is in understudied
populations such as those of from Latin America. To fill in this gap we created the Latin American Research
Consortium on the Genetics of PD (LARGE-PD), a growing collaboration between thirty two institutions in
eleven countries across South America/Caribe (Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador,
Honduras, Mexico, Peru, Puerto Rico and Uruguay). LARGE-PD is the largest PD case-control sample series
in Latin America (3,857 individuals), with a target to include at least 8,000 individuals in by 2021, thus serving
as a unique resource for genetic analysis in this understudied population. As LARGE-PD has progressed,
several multiplex PD families (with three or more affected individuals) have been identified and enrolled. With
the goal of replicating our preliminary findings and identifying novel risk-modifying variants we propose in Aim 1
to perform a Genome-Wide Association Study (GWAS) in an additional 6,000 cases and healthy controls (1:1)
ascertained through LARGE-PD. Our preliminary study in a subset of LARGE-PD (N=1,498) identified 7
interesting novel candidate loci. Genotyping this additional 6,000 individuals (N= 7,498) allows replication of
these findings and quadruples our statistical power to find novel associations. We will also perform the first
trans-ethnic GWAS in collaboration with the largest European consortium. In Aim 2, we will perform Whole-
Genome Sequencing (WGS) in 25 LARGE-PD families negative for mutations in all known PD-genes. Finally,
in Aim 3 we will use all our data to generate and test a Latino specific Polygenic Risk Score (PRS), which will
account for possible additive effects between all associated variants and will help improve PD risk prediction in
this population.
 This project will identify novel PD genes associated with both familial and sporadic forms of PD using an
understudied population, thus improving our knowledge of the etiopatogenesis of the disease and identifying
novel therapeutic targets for the treatment of PD, not only in Latin America, but also in other countries with a
growing Latino population such as the US. We will also test the validity of current PD risk prediction, based on
European populations, in Latinos and generate a Latino specific risk score using our data. We also believe that
our study and others like it, will reduce existing health disparities by allowing Latinos to be active participants in
clinical trials and novel treatments designed to protect and/...

## Key facts

- **NIH application ID:** 10927296
- **Project number:** 5R01NS112499-05
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Ignacio Fernandez Mata
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $589,629
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10927296

## Citation

> US National Institutes of Health, RePORTER application 10927296, Identifying novel Parkinson'’s disease genes exploring understudied Latino populations (5R01NS112499-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10927296. Licensed CC0.

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