# Innovative approaches to elucidate the genetic etiology of age-related hearing impairment and tinnitus

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $534,236

## Abstract

SUMMARY
 To investigate the genetic basis of age-related hearing impairment (ARHI) and tinnitus we will analyze
genotype array, whole genome imputed and exome sequence data from 500,000 participants in the UK
Biobank. We will conduct single and rare variant aggregate association tests: testing for main effects, sex and
age specific associations and interactions (gene x gene; gene x environment; gene x age; gene x age; and
gene x sex) controlling for important confounders, e.g. noise exposure. We perform fine mapping to tease
apart functional causal variants from those which are in linkage disequilibrium. We will also test for pleiotropy
and perform mediation analysis to determine if biological or mediated pleiotropy has been detected.
Additionally, we plan to develop novel approaches to analyze imputed genetic data that explicitly account for
the uncertainty in genotype calls during association analysis. By ignoring or improperly modeling the
uncertainty in imputed genotypes, current methods suffer from a decreased ability to detect associations as
well as an increased false positive findings rate. Therefore, we will develop methods to analyze imputed data,
which properly models imputed genotype data uncertainty to allow for the detection of associations,
interactions, pleiotropy and fine mapping. The novel methods will be thoroughly evaluated and implemented in
our SEQSpark software to perform data quality control, annotation, and association analysis for hundreds of
thousands of samples with imputed genotype data. This study has the potential for significant public health
impact by providing a useful analytic tool to the research community and by conducting a well-powered,
comprehensive investigation of the genetic etiology of ARHI and tinnitus which in turn will aid in risk prediction,
prevention, and improved and new treatment modalities.

## Key facts

- **NIH application ID:** 10001464
- **Project number:** 5R01DC017712-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Paul L. Auer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $534,236
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001464

## Citation

> US National Institutes of Health, RePORTER application 10001464, Innovative approaches to elucidate the genetic etiology of age-related hearing impairment and tinnitus (5R01DC017712-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001464. Licensed CC0.

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