More than 25% of individuals over age 65 and 50% of individuals over age 80 suffer from varying levels of age- related hearing impairment (AHRI), and adults are losing hearing at earlier ages than in the past. Age-related hearing impairment can make it difficult to communicate and understand speech, and can lead to an overall lower quality of life. Thus it is an important public health concern. There is strong evidence that both genetic and environmental factors play a role in age-related hearing impairment. Although there have been some studies on the genetics of age-related hearing disorders, they have been on limited sample sizes and have not fully explained the heritability of the disease. A previous genome-wide association study of 1,692 individuals implicated one gene, and study of hearing thresholds on 3,417 individuals provided several candidates for further observation. Here we propose a genome-wide association study that is orders of magnitude larger than previous studies in a cohort of 100,000 individuals nested in the Kaiser Research Program on Genes, Environment, and Health. These individuals have a mean age of 63, and already have genome-wide data at over 650,000 single nucleotide polymorphisms (SNPs). We expect that with such a large cohort, we will have much more power to detect loci that affect age-related hearing loss, that may lead to discoveries of additional genes that affect hearing loss. This project provides an efficient and innovative opportunity to obtain a comprehensive understanding of how these genetic factors impact AHRI, which may help identify individuals at greater risk so they can take more preventative measures. Understanding the genetic factors will also lead to better understanding of the underlying biological mechanisms of AHRI, which may improve potential treatments.

Public Health Relevance

Age-related hearing loss is the most common sensory impairment in the elderly, but finding mechanisms underlying this disease has been difficult. Our efforts towards understanding the genetic basis of age-related hearing loss will help in identifying individuals at greater risk, will improve understanding of the disease, and thereby improve our overall health.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DC013300-02
Application #
8675831
Study Section
Communication Disorders Review Committee (CDRC)
Program Officer
Sklare, Dan
Project Start
2013-07-01
Project End
2018-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Hoffmann, Thomas J; Theusch, Elizabeth; Haldar, Tanushree et al. (2018) A large electronic-health-record-based genome-wide study of serum lipids. Nat Genet 50:401-413
Hoffmann, Thomas J; Keats, Bronya J; Yoshikawa, Noriko et al. (2016) A Large Genome-Wide Association Study of Age-Related Hearing Impairment Using Electronic Health Records. PLoS Genet 12:e1006371
Hoffmann, Thomas J; Van Den Eeden, Stephen K; Sakoda, Lori C et al. (2015) A large multiethnic genome-wide association study of prostate cancer identifies novel risk variants and substantial ethnic differences. Cancer Discov 5:878-91
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Hoffmann, Thomas J; Sakoda, Lori C; Shen, Ling et al. (2015) Imputation of the rare HOXB13 G84E mutation and cancer risk in a large population-based cohort. PLoS Genet 11:e1004930