# Project 1:  Identification of susceptibility genes for age-related hearing loss

> **NIH NIH P50** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2022 · $350,814

## Abstract

PROJECT SUMMARY/ABSTRACT – PROJECT 1
 Age-related hearing loss (presbyacusis) is a consequence of accumulated environmental stresses to
the inner ear and an intrinsic genetically controlled aging process, with as much as 60% of hearing loss in older
adults attributable to heritability. The often uncertain medical and noise exposure histories in human subjects
coupled with the high variability in the age of onset, rate of progression and the nature and severity of the
hearing loss make it difficult to attribute presbyacusis to a specific cause. Moreover, this phenotypic variability
and other characteristics strongly suggest that age-related hearing loss is a complex polygenic disorder
possibly involving different alleles on multiple genes, although in some instances, it could result from a
mutation(s) in a single gene. Advances in next generation sequencing have provided a powerful new tool to
address the genetic basis of many age-related diseases. Here we continue to investigate the genetic,
molecular and cellular basis of human presbyacusis. Project 1 takes advantage of the Center's extensive and
continuously growing database (Core B) containing well documented medical and noise exposure histories
and auditory function measures along with DNA samples from large numbers of human subjects. It also
capitalizes on the development of new algorithms based on audiograms and data from animal models to define
specific age-related hearing loss phenotypes in our subjects. Accordingly, we will perform a comprehensive
population-based cohort molecular genetic study to provide information about genetic contributions to specific
auditory phenotypes and biological pathways involved with age-related hearing loss. Aim 1.1 continues to
identify and validate genetic variants associated with increased susceptibility to presbyacusis by employing
molecular genetic analyses using whole exome sequence data from a replication cohort of ≥55 year old
subjects of non-Finnish European ancestry and an African ancestry cohort. This aim will also investigate
causal relationships between specific genetic variants and hearing loss via functional and histopathological
analyses of mouse lines generated by knock-in or knock-out of specific candidate genetic variants. Aim 1.2
determines the pathological and potential functional consequences of genetic variants causing age-related
hearing loss by assessing the distribution and changes in the expression pattern of promising candidate gene
products and their association with pathological changes in human temporal bones.

## Key facts

- **NIH application ID:** 10470231
- **Project number:** 5P50DC000422-34
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** BRAD SCHULTE
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $350,814
- **Award type:** 5
- **Project period:** 1997-07-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10470231

## Citation

> US National Institutes of Health, RePORTER application 10470231, Project 1:  Identification of susceptibility genes for age-related hearing loss (5P50DC000422-34). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10470231. Licensed CC0.

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