NASHVILLE, TENNESSEE — Researchers at Vanderbilt University Medical Center have found that combining genetic information with detailed hearing test results may improve the ability to identify genetic factors associated with hearing loss, potentially opening the door to earlier detection and more personalized hearing healthcare.
The study, published October 8, 2026, in JAMA Otolaryngology–Head & Neck Surgery, found that using audiometric measurements rather than traditional medical diagnostic codes allowed researchers to identify genetic associations that would otherwise have been missed.
By linking clinical audiograms with genetic information from thousands of patients, the Vanderbilt team demonstrated that more precise measurements of hearing sensitivity could improve genetic discovery and estimates of hearing loss risk.
Looking Beyond Traditional Hearing Loss Diagnoses
Hearing loss is influenced by a combination of genetic, environmental, and age-related factors. Although researchers have identified numerous genes associated with inherited forms of hearing loss, understanding the genetic contributions to hearing difficulties across the broader population remains challenging.
One obstacle is how hearing loss is classified in large medical databases.
Genetic studies frequently rely on diagnostic codes recorded in electronic health records. These codes can identify whether someone has received a hearing loss diagnosis, but they generally provide limited information about the degree, configuration, or specific frequencies affected.
Two individuals with substantially different hearing abilities may therefore be grouped under the same diagnostic category, potentially obscuring important genetic differences.
To address this limitation, the Vanderbilt researchers investigated an approach known as precision phenotyping, which uses detailed, quantitative clinical measurements to characterize a health condition rather than relying solely on broad diagnostic categories.
In this case, the researchers used pure-tone audiometric thresholds to provide a more precise representation of hearing sensitivity.
Analyzing Hearing Tests and Genetic Data
The research team used Vanderbilt’s BioVU biobank, which links deidentified genetic information with clinical health records, to compare two approaches to identifying genetic associations with sensorineural hearing loss.
The first analysis included approximately 61,500 individuals whose hearing status was classified using medical diagnostic codes. The second included 16,057 individuals with available pure-tone audiometric measurements.
For the audiometry-based analysis, researchers calculated pure-tone averages using hearing thresholds at 500, 1,000, and 2,000 Hz in the better-hearing ear. These measurements allowed hearing sensitivity to be analyzed along a continuous scale rather than simply classifying individuals as having or not having hearing loss.
Both approaches were evaluated using genome-wide association studies, which examine genetic variations across large populations to identify associations with particular characteristics or health conditions.
Despite including substantially fewer participants, the audiometry-based analysis produced stronger genetic findings.
Four Genes Associated With Hearing Sensitivity
The researchers identified three statistically significant genetic regions associated with four genes: EML6, SPTBN1, ARHGEF28, and EYA4.
These genes have biological functions related to nervous system development, cellular signaling, or auditory function. EYA4, for example, has previously been associated with certain forms of nonsyndromic sensorineural hearing loss.
In contrast, the larger analysis based on diagnostic codes did not identify any genetic regions reaching the study’s threshold for genome-wide statistical significance.
The researchers also found that the audiometry-based approach produced a substantially higher estimate of the proportion of hearing sensitivity differences associated with the common genetic variants examined. The estimate was approximately 12%, compared with about 3% using diagnostic codes.
These findings suggest that more detailed hearing measurements may help researchers detect genetic influences that become difficult to identify when hearing loss is treated as a simple yes-or-no diagnosis.
Improving Genetic Risk Prediction
Beyond identifying genetic associations, the team investigated whether the findings could improve estimates of an individual’s genetic susceptibility to hearing loss.
Researchers developed polygenic risk scores, which combine information from many genetic variants to estimate a person’s relative genetic predisposition to a particular condition.
They then evaluated the scores using an independent dataset from the National Institutes of Health’s All of Us Research Program, including more than 109,000 participants with hearing-related survey information.
The risk scores developed using audiometric measurements showed stronger associations with self-reported hearing difficulties than scores developed using diagnostic codes.
In Vanderbilt’s announcement, study co-first author Andie DeFreese, AuD, a clinical audiologist and PhD candidate in the Department of Hearing and Speech Sciences, explained that the findings highlight the value of more precise clinical information when studying the genetics of hearing loss.
“The purpose of our study was to understand the genetic architecture of sensorineural hearing loss. Long term, we want to be able to identify our patients with hearing loss before it ever emerges.”
DeFreese also emphasized that the findings could have implications beyond hearing healthcare, particularly for medical research that relies on large databases containing relatively broad diagnostic information.
Could Genetic Testing Identify Hearing Loss Earlier?
One potential long-term application of this research is the development of tools that could identify individuals at increased risk for hearing loss before noticeable communication difficulties arise.
Such tools might eventually help clinicians recommend more individualized monitoring, preventive strategies, or earlier interventions based on a combination of genetic information and clinical findings.
However, the study does not establish that genetic testing can currently predict when a particular individual will develop hearing loss.
The researchers evaluated genetic associations and risk scores rather than following initially unaffected individuals over time to determine who subsequently developed hearing loss. The genetic analyses were also restricted to individuals of European genetic ancestry, limiting how broadly the findings can currently be applied.
Additionally, the audiometric measurements used in the study were based on three frequencies in the better-hearing ear. Although this approach provides a standardized measure of hearing sensitivity, it does not capture every aspect of hearing function, including high-frequency hearing difficulties or speech understanding in noise.
Further research will be needed to determine whether more comprehensive hearing measurements and genetic models can reliably predict future hearing outcomes across diverse populations.
Potential Implications for Hearing Healthcare
The findings also reinforce the importance of detailed clinical audiometric data in advancing hearing research.
While diagnostic codes remain useful for documenting medical conditions, audiograms provide information about hearing sensitivity that may be particularly valuable when investigating genetic influences.
For audiologists and other hearing care professionals, the research suggests that routine clinical measurements could contribute to broader scientific discoveries when appropriately integrated with genetic databases.
The work also comes amid growing interest in genetic and precision-medicine approaches to hearing disorders, including emerging gene-based treatments for certain inherited forms of hearing loss.
Study corresponding author Taha Jan, MD, an assistant professor of Otolaryngology–Head and Neck Surgery at Vanderbilt, highlighted the increasing relevance of genetics to the future of hearing healthcare.
Although clinical applications remain a longer-term goal, the Vanderbilt findings provide evidence that more precisely characterizing hearing sensitivity can improve the identification of genetic associations and strengthen research into individualized hearing loss risk.
Rather than relying solely on whether someone has a hearing loss diagnosis, the research suggests that understanding how well someone hears may be an important step toward understanding why hearing loss develops and who may be most susceptible.
References
1. DeFreese AJ, Rubat du Mérac T, Sheng Q, Nayak S, Jan TA. Precision Phenotyping With Audiometric Data and Gene Discovery for Sensorineural Hearing Loss. JAMA Otolaryngology–Head & Neck Surgery. Published online October 8, 2026. https://doi.org/10.1001/jamaoto.2026.3089
2. Vanderbilt University Medical Center. New Genetic Insights Could Help Detect Hearing Loss Earlier. October 8, 2026. Vanderbilt Health News.
