# Genome-wide Investigation of the Interplay Between Age-Related Hearing Loss and Smoking Behaviors

> **NIH NIH R21** · YALE UNIVERSITY · 2021 · $144,013

## Abstract

ABSTRACT. Age-related hearing loss is a common disorder defined as the loss of the hearing
with aging. In the United States, approximately 33% of the population between ages of 65 and 74
are subjected to hearing loss, and after 75 years of age, about 50% of the population have hearing
problems. There are many causes of age-related hearing loss, including age-induced changes in
the in the inner and middle ear and also complex changes along the nerve pathways from the ear
to the brain. Epidemiological studies, such as The Epidemiology of Hearing Loss Study and
National Health and Nutrition Examination Survey 1999-2004, have shown that the major risk
factors for age-related hearing loss are noise exposure and smoking. Very limited information is
available regarding the molecular pathways involved in age-related hearing loss and how smoking
behaviors increase its risk. Our previous results suggest that genetic variation can play a role in
moderating the effect of smoking on age-related hearing loss reducing smoking-induced damage
in brain regions involved in auditory function. In the current proposal, we will apply genome-wide
approaches to identify additional mechanisms involved in the age-related hearing loss induced
by smoking behaviors. Specifically, we will conduct a genome-wide association study of age-
related hearing loss in more than 500,000 subjects (>150,000 nicotine-exposed, >350,000
nicotine-unexposed). We will use the genetic and phenotypic information from cohorts from the
UK Biobank, the Nurses' Health Studies I and II, the Health Professionals Follow-Up Study, and
the National Center for Biotechnology Information the database of Genotypes and Phenotypes to
conduct a genome-wide association study of hearing loss in individuals exposed to nicotine. A
follow-up study will be performed with respect brain structure and activity using magnetic
resonance imaging data from the UK Biobank. Additionally, we will conduct a multivariable
Mendelian Randomization to investigate which metabolomic alterations and/or brain-structure
changes mediate the causal relationship between smoking and hearing loss. The goal of this
analysis is to verify the causal effect and the mediation processes involved in the interplay
between smoking behaviors and hearing loss. The expected findings will provide novel insights
regarding the molecular mechanisms by which smoking behaviors cause age-related hearing loss
A better understanding of its genetics could permit us to develop more effective preventive
strategies and therapeutic approaches that can improve the quality of life of the growing elderly
population.

## Key facts

- **NIH application ID:** 10237374
- **Project number:** 5R21DC018098-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** RENATO POLIMANTI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $144,013
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10237374

## Citation

> US National Institutes of Health, RePORTER application 10237374, Genome-wide Investigation of the Interplay Between Age-Related Hearing Loss and Smoking Behaviors (5R21DC018098-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10237374. Licensed CC0.

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