# Genetic and epigenomic determinants of hearing loss in Hispanic populations

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2023 · $75,618

## Abstract

ABSTRACT [originally submitted with R01DC019642 and included here with minimal modifications]:
Sensorineural hearing loss (SNHL) is a leading cause of disability and affects ~1.4 billion people globally,
including different age groups and ethnicities. Although around 150 genes have been identified for SNHL, the
Hispanic population remains understudied for SNHL, with most Hispanic studies focused on a single gene GJB2.
A few countries studied – Chile, Mexico/Hispanic-American, the Philippines – have a low prevalence of GJB2
variants, suggesting that SNHL cohorts from these countries have novel genes or variants for discovery.
Additionally, Hispanic children are at risk for environmental exposures to chemicals that may lead to epigenetic
modifications and cause SNHL. Our overarching hypothesis is that SNHL has a unique, population-specific
allelic and epigenetic spectrum in Hispanic-descent populations. We assembled an international group of
researchers with complementary expertise in otology, genetics, epigenomics and functional genomics, with
previous collaborative experience that signals this project will be highly productive. In our previous studies, we
identified novel variants in Hispanic-American and Filipino patients with SNHL, including genetic variants that
were associated with temporal bone anomalies and predictive of cochlear implant outcomes. We have in place
efficient pipelines for the identification of novel SNHL genes in families and differentially methylated regions
(DMRs) in case-control cohorts, as well as validation methods in animal models and epithelial cells. Our goal is
to determine genetic and epigenetic risk factors in Hispanic children with SNHL. For Aim 1, we will identify
SNHL variants from next-generation sequence data using a tiered approach, which includes Sanger sequencing,
filtering, homozygosity mapping, linkage analysis and transmission disequilibrium tests. We will recruit 500
Hispanic families, including large families sufficient for genome-wide significant linkage, and submit DNA
samples to sequencing and analyses. Novel SNHL genes and variants identified in these families will be followed
up with protein localization and hearing studies in mouse and zebrafish models, and mutation constructs in
epithelial cells. For Aim 2, we will perform an epigenome-wide association study by profiling the methylome of a
well-powered cohort of 500 SNHL probands and 500 hearing children matched by age, sex and population, in
order to identify DMRs that are associated with SNHL. For the top identified DMRs, we will utilize CRISPR-dCas9
technology on epithelial cells to determine if targeting the methylation site will affect gene expression. Integration
of methylation profiles and genetic data using methylation quantitative trait locus analysis will aid in
understanding genetic vs. environmental contributions to SNHL. Overall, this project will impact genetic
screening protocols and genetic counseling particularly in Hispanic po...

## Key facts

- **NIH application ID:** 10687642
- **Project number:** 3R01DC019642-02S1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Regie Lyn Pastor Santos-Cortez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $75,618
- **Award type:** 3
- **Project period:** 2022-09-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10687642

## Citation

> US National Institutes of Health, RePORTER application 10687642, Genetic and epigenomic determinants of hearing loss in Hispanic populations (3R01DC019642-02S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10687642. Licensed CC0.

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