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Polygenic Risk Score-Based Association Analysis of Speech-in-Noise and Hearing Threshold Measures in Healthy Young Adults with Self-reported Normal Hearing

Journal of the Association for Research in Otolaryngology (2023)Cite this article

Abstract

Purpose

Speech-in-noise (SIN) traits exhibit high inter-subject variability, even for healthy young adults reporting normal hearing. Emerging evidence suggests that genetic variability could influence inter-subject variability in SIN traits. Genome-wide association studies (GWAS) have uncovered the polygenic architecture of various adult-onset complex human conditions. Polygenic risk scores (PRS) summarize complex genetic susceptibility to quantify the degree of genetic risk for health conditions. The present study conducted PRS-based association analyses to identify PRS risk factors for SIN and hearing threshold measures in 255 healthy young adults (18–40 years) with self-reported normal hearing.

Methods

Self-reported SIN perception abilities were assessed by the Speech, Spatial, and Qualities of Hearing Scale (SSQ12). QuickSIN and audiometry (0.25–16 kHz) were performed on 218 participants. Saliva-derived DNA was used for low-pass whole genome sequencing, and 2620 PRS variables for various traits were calculated using the models derived from the polygenic risk score (PGS) catalog. The regression analysis was conducted to identify predictors for SSQ12, QuickSIN, and better ear puretone averages at conventional (PTA0.5–2), high (PTA4-8), and extended-high (PTA12.5–16) frequency ranges.

Results

Participants with a higher genetic predisposition to HDL cholesterol reported better SSQ12. Participants with high PRS to dementia revealed significantly elevated PTA4-8, and those with high PRS to atrial fibrillation and flutter revealed significantly elevated PTA12.5–16.

Conclusion

These results indicate that healthy individuals with polygenic risk of certain health conditions could exhibit a subclinical decline in hearing health measures at young ages, decades before clinically meaningful SIN deficits and hearing loss could be observed. PRS could be used to identify high-risk individuals to prevent hearing health conditions by promoting a healthy lifestyle.

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Data Availability

The database will be available on NIH dbGaP after the completion of the project R21DC016704-01A1.

Abbreviations

PRS:

Polygenic risk score

GWAS:

Genome-wide association study

SNP:

Single nucleotide polymorphism

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Acknowledgements

We thank Jeff Lane, Megan Booth, Sarah Kingsbury, Hailey Kingsbury, Klayre Michel, Kila Haney, Qiayi He, Madeline McCarville, and Miranda Becker for their assistance in data collection and handling.

Funding

The study was funded by the National Institute on Deafness and Other Communication Disorders Grant R21DC016704-01A1.

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Authors and Affiliations

  1. Department of Communication Sciences & Disorders, University of Iowa, 250 Hawkins Dr, Iowa City, IA, 52242, USA

    Ishan Sunilkumar Bhatt, Sai Kumar Ramadugu, Shawn Goodman, Srividya Grama Bhagavan & Valerie Ingalls

  2. Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, 32608, USA

    Raquel Dias

  3. Department of Integrative Structural and Computational Biology, Scripps Science Institute, La Jolla, CA, 92037, USA

    Ali Torkamani

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  1. Ishan Sunilkumar Bhatt
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  2. Sai Kumar Ramadugu
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Correspondence to Ishan Sunilkumar Bhatt.

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Bhatt, I.S., Ramadugu, S.K., Goodman, S. et al. Polygenic Risk Score-Based Association Analysis of Speech-in-Noise and Hearing Threshold Measures in Healthy Young Adults with Self-reported Normal Hearing. JARO (2023). https://doi.org/10.1007/s10162-023-00911-4

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