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

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $406,740

## Abstract

ABSTRACT
In 2020, ~5.8 million Americans suffered from Alzheimer’s disease (AD) of which ~5.6 million had
late-onset AD (LOAD). One in 10 Americans age >65 has AD. Although >30 genes have been
implicated in LOAD etiology, many more remain to be discovered. For many of these associations
the causal variant has yet to be identified. Additionally, little is known how genes and genes and
sex interact to increase susceptibility to LOAD. It has been shown that there is an association
between AD and age-related hearing impairment (ARHI) and AD and tinnitus. However, it is
unknown whether this association is driven by shared genetic risk factors (i.e. pleiotropy). Through
the parent grant on ARHI and tinnitus we have developed a framework to study interactions and
pleiotropy that can be applied to AD to bring about a better understanding of its etiology. As in the
parent grant, the UK Biobank, one of the largest population-based studies available to the
scientific community with extensive phenotype and genetic data on ~500,000 study subjects, will
be analyzed. The findings will be replicated using an AD specific data set which contains 19,379
cases and 22,495 controls of African-American, Hispanic, and European ancestry who also have
data on ARHI. For the UK Biobank, machine learning and data on >6,000 phenotypes,
environmental exposures, cognitive measures, etc. will be used to generate AD probability scores,
that will be used as a proxy for AD status. We will analyze these datasets for AD main effects and
variant (v) x v, gene (g) x v, g x g, v x sex (s), and g x s interactions. For the replicated associations,
fine-mapping will be performed using Bayesian credible set. For associations detected for ARHI
and tinnitus in the parent grant, it will be determined if the same variants are associated with AD
and ARHI and AD and tinnitus. For these variants, mediation analysis will be performed to
determine if the observed pleiotropy is mediated or biological. This study should provide better
insight into the genetic etiology of AD and the role of interaction in AD susceptibility as well an
improved understanding of the relationship between AD, ARHI, and tinnitus.

## Key facts

- **NIH application ID:** 10497412
- **Project number:** 3R01DC017712-03S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Andrew DeWan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $406,740
- **Award type:** 3
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10497412

## Citation

> US National Institutes of Health, RePORTER application 10497412, Innovative approaches to elucidate the genetic etiology of age-related hearing impairment and tinnitus (3R01DC017712-03S1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10497412. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*