Approved Research

Development of a Polygenic Risk Score (PRS) for Age-related Hearing Loss and Tinnitus

Lay summary

Hearing loss and tinnitus (ringing or buzzing in the absence of external stimuli) are common chronic health conditions particularly impacting older adults throughout the world. In addition to the negative impact of these health conditions on one's quality of life, they are associated with cognitive decline and dementia. The aim of our research is to identify how one's DNA predisposes an individual for age-related hearing loss or tinnitus. Identifying genes (and genetic variation) that play a role in hearing loss and tinnitus allows for the eventual development of drugs and/or personalized treatment to prevent or treat these health conditions. For a more rigorous study, we will use large datasets available to us in the United States (250,000 participants) to discover genetic variation contributing to hearing loss and tinnitus and then use the UK Biobank dataset (291,516 participants) to validate our findings. Once we establish the DNA associated with hearing loss and tinnitus, we can study whether the same DNA variation is also associated with hearing loss and tinnitus following certain chemotherapy or radiation to the brain as well as other health conditions, such as diabetes, anxiety, or Alzheimer's dementia. The project will take one year. The public health impact is that the findings can ultimately help the 430 million people worldwide who live with disabling hearing loss.

Scope extension:

1. To utilize UK Biobank as a replication cohort for our genome wide association study (GWAS) of age-related hearing loss and de novo tinnitus comprised of 2 genotyped cohorts associated with electronic health records: 40,000 participants in Electronic Medical Records and Genomics network (eMERGE) and 60,000 participants in Vanderbilts collection of de-identified DNA samples linked to Electronic Health Records (BioVu).
2. To evaluate the validity of a Polygenic Risk Score created from our GWAS of age-related hearing loss and GWAS of de novo tinnitus on 100,000 individuals in UK Biobank GWAS of hearing loss and tinnitus, respectively.
3. To utilize UK Biobank Digit Triplet Test data as a replication set for our GWAS of speech recognition threshold on 2,000 individuals.
4. To evaluate shared genetic architecture of age-related ototoxicity with cancer treatment-related ototoxicity and other age-related phenotypes including dementia.
5. To perform a GWAS of de novo tinnitus using UK biobank data.
6. To perform GWAS of hearing difficulty and GWAS of hearing loss using UK biobank data.
7. To use GWAS results (aims 5 and 6) for building and evaluation of PRS models for these conditions and to study the shared genetic architecture with conditions listed at aim 4.