Dissertation
Uncovering genetic comorbidities of speech-in-noise deficits using polygenic risk score analysis from two independent cohorts
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Spring 2025
DOI: 10.25820/etd.008004
Abstract
Objective: Understanding speech in noisy environments is a crucial aspect of daily communication, and difficulties in this ability, known as speech-in-noise (SIN) deficits, can occur even in individuals with clinically normal hearing sensitivity. This study aimed to investigate the genetic comorbidities of SIN deficits by employing a polygenic risk score (PRS) analysis across two independent cohorts. PRS summarizes a complex genetic inheritance of health conditions or traits into a single score. The primary objective was to identify PRS predictors across the health spectrum associated with SIN deficits.Method: The study utilized two independent cohorts - the UK Biobank (N=343,104) served as the discovery sample, where SIN deficits were defined based on self-reported hearing difficulty in noise but self-reported normal hearing in quiet. The AudioGEN cohort (N=228), comprising healthy young adults with self-reported normal hearing, served as the replication sample. SIN deficits were measured using the Speech, Spatial, and Qualities of Hearing scale (SSQ12), QuickSIN, and 3-digit dichotic digit test (DDT). PRS were calculated for 2627 common health conditions and disease phenotypes from the polygenic risk score (PGS) catalog. Statistical analysis involved logistic regression in the UK Biobank to identify PRS predictors of SIN deficits, and linear mixed models (LMM) in the AudioGEN cohort to evaluate the association between PRS predictors and SIN measures, adjusting for relevant covariates. Enrichment analysis was performed to determine if PRS predictors associated with SIN deficits were over-represented in specific trait categories.
Results: In the UK Biobank, 449 PRS predictors across various health categories showed statistically significant associations with self-reported SIN deficits (FDR p < 0.05). Replication analysis in the AudioGEN cohort revealed 84 PRS predictors replicated for SSQ12, 22 for QuickSIN, and one for DDT. Enrichment analysis revealed a significant overrepresentation of PRS predictors related to mental health, lifestyle, and sleep-related traits among individuals significantly associated with SIN deficits in the UK Biobank sample.
Discussion and conclusion: The findings of this study suggest a shared genetic basis between SIN deficits and a broad range of health conditions, with a notable enrichment for mental health traits. The successful replication of several PRS predictors across two independent cohorts and different measures of SIN perception strengthens these associations. The results are consistent with the polygenic inheritance of SIN deficits. Further research is warranted to elucidate the biological mechanisms underlying these genetic comorbidities and their implications for treating SIN deficits.
Details
- Title: Subtitle
- Uncovering genetic comorbidities of speech-in-noise deficits using polygenic risk score analysis from two independent cohorts
- Creators
- Srividya Grama Bhagavan
- Contributors
- Ishan Bhatt (Advisor)Inyong Choi (Committee Member)Shawn Goodman (Committee Member)Joel Berger (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Speech and Hearing Science
- Date degree season
- Spring 2025
- DOI
- 10.25820/etd.008004
- Publisher
- University of Iowa
- Number of pages
- xii, 140 pages
- Copyright
- Copyright 2025 Srividya Grama Bhagavan
- Language
- English
- Date submitted
- 04/28/2025
- Description illustrations
- color illustrations
- Description bibliographic
- Includes bibliographical references (page 115-140).
- Public Abstract (ETD)
Have you ever struggled to hear a conversation in a busy restaurant, even though your hearing seems fine in quiet places? Many people experience this difficulty, known as speech-in-noise (SIN) deficits, despite having normal hearing. While we know that both the brain and ears play a role in processing speech, researchers are still trying to understand why some individuals have more trouble than others. This study looks at the genetic reasons why some people have more trouble hearing SIN. We wanted to see if the genes that are linked to other health conditions might also play a role in this common listening problem. We looked at the genetic information of hundreds of thousands of people in a large dataset called the UK Biobank and compared those who said they had difficulty hearing in noise to those who did not. We then checked our findings in a smaller group of younger adults who had normal hearing.
Our research found that genes associated with various health conditions are linked to SIN deficits. Interestingly, we found a strong connection between genes related to mental health, like anxiety and worry, and problems understanding SIN. This suggests that the same underlying genetic factors might affect both our mental well-being and our ability to process SIN. This study helps us understand that the ability to hear in noise is influenced by genes that affect other aspects of our health, especially our mental health. This knowledge could eventually lead to a better understanding of why some people struggle in noisy environments and why some do not, potentially identify those at risk before they acquire SIN deficits, design individualized prevention plans, may help in developing better hearing tests, personalized treatment approaches, and early interventions for those at risk of SIN deficits. Ultimately, understanding the genetics behind SIN perception can improve communication and quality of life for many people.
- Academic Unit
- Communication Sciences and Disorders
- Record Identifier
- 9984831229702771
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