Polygenic Risk Scores and Hearing Loss Phenotypes in Children

Jing Wang^{1

2}, Fan He^{1

3

4}, Daisy A Shepherd^{1

2}, Shuai Li^{1

5

6

7}, Katherine Lange^{1

2}, Valerie Sung^{1

2

8}, Angela Morgan^{1

9

10}, Jessica A Kerr^{1

2

11}, Richard Saffery^{1

2}, Melissa Wake^{1

2

12}

Affiliations

¹ Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.
² Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
³ John Richards Centre for Rural Ageing Research, La Trobe Rural Health School, College of Science, Health and Engineering, La Trobe University.
⁴ Centre for Cancer Research, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
⁵ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
⁶ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
⁷ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
⁸ Centre for Community Child Health, Royal Children's Hospital, Parkville, Victoria, Australia.
⁹ Department of Audiology and Speech Pathology, The University of Melbourne, Parkville, Victoria, Australia.
¹⁰ Speech Pathology Department, Royal Children's Hospital, Parkville, Victoria, Australia.
¹¹ Department of Psychological Medicine, University of Otago, Christchurch, New Zealand.
¹² Department of Paediatrics & The Liggins Institute, The University of Auckland, Grafton, Auckland, New Zealand.

PMID: 39509092
PMCID: PMC11544553 (available on 2025-11-07)
DOI: 10.1001/jamaoto.2024.3659

Polygenic Risk Scores and Hearing Loss Phenotypes in Children

Jing Wang et al. JAMA Otolaryngol Head Neck Surg. 2024.

. 2024 Nov 7;151(1):56-64.

doi: 10.1001/jamaoto.2024.3659. Online ahead of print.

Authors

Affiliations

¹ Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.
² Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
³ John Richards Centre for Rural Ageing Research, La Trobe Rural Health School, College of Science, Health and Engineering, La Trobe University.
⁴ Centre for Cancer Research, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
⁵ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
⁶ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
⁷ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
⁸ Centre for Community Child Health, Royal Children's Hospital, Parkville, Victoria, Australia.
⁹ Department of Audiology and Speech Pathology, The University of Melbourne, Parkville, Victoria, Australia.
¹⁰ Speech Pathology Department, Royal Children's Hospital, Parkville, Victoria, Australia.
¹¹ Department of Psychological Medicine, University of Otago, Christchurch, New Zealand.
¹² Department of Paediatrics & The Liggins Institute, The University of Auckland, Grafton, Auckland, New Zealand.

PMID: 39509092
PMCID: PMC11544553 (available on 2025-11-07)
DOI: 10.1001/jamaoto.2024.3659

Abstract

Importance: Monogenic causes of childhood hearing loss are well established, as are polygenic risk contributions to age-related hearing loss. However, an untested possibility is that polygenic risk scores (PRS) also contribute to childhood hearing loss of all severities, alongside environmental and/or monogenic causes.

Objective: To examine the association between a PRS for adult hearing loss and childhood hearing loss phenotypes.

Design, setting, and participants: This cross-sectional study used a unique population-based dataset spanning normal hearing to profound loss, combining 2 contemporaneous population cohorts in Australia. This included the Child Health CheckPoint, a national population-based cross-sectional study nested within the Longitudinal Study of Australian Children, and the Victorian Childhood Hearing Longitudinal Databank (VicCHILD), a statewide population-based longitudinal data bank open to every child with congenital hearing loss in Victoria, Australia. The analysis took place from March to August 2023.

Exposures: Genotype data were generated from saliva- or blood-derived DNA using global single-nucleotide variations arrays. Based on genotype data, PRS was computed using published UK Biobank genome-wide association study results for self-reported hearing difficulty in individuals aged 40 to 69 years.

Main outcomes and measures: Hearing outcomes were classified by laterality (bilateral, unilateral), severity (mild, moderate, severe or worse) and types (sensorineural, conductive, mixed, auditory neuropathy, atresia). Analyses included multinominal logistic regressions of PRS with hearing outcomes.

Results: Overall, 1488 CheckPoint study children (49.8% boys, aged 11-12 years) and 527 VicCHILD study children (55.2% boys, aged 0-13 years) with hearing and genotype data were included. A 1-SD increment in PRS was associated with higher odds of mild (odds ratio [OR], 1.3; 95% CI, 1.0-1.6), moderate (OR, 5.1; 95% CI, 3.2-8.1), and severe or worse (OR, 5.3; 95% CI, 3.9-7.3) unilateral hearing loss compared with normal hearing. Similarly, the PRS was associated with increased odds of mild, moderate, and severe or worse bilateral hearing loss (per-SD ORs, 3.9-6.6) and all hearing loss types (per-SD ORs, 8.5-10.6).

Conclusions and relevance: In this cross-sectional study, a PRS initially developed for adult hearing difficulty was associated with wide-ranging childhood hearing loss phenotypes, partly explaining hearing phenotype variations despite shared genetic and environmental factors (eg, preterm birth). Large-scale studies with objectively defined hearing phenotypes are crucial for refining PRS and predicting high-risk children.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Li reported grants from the Australian National Health and Medical Research Council (NHMRC) outside the submitted work. Dr Wake reported grants from NHMRC as funding to undertake the Child Health CheckPoint and fellowship grants from NHMRC funding for salary to lead the CheckPoint and VicCHILD initiatives during the conduct of the study; competitive academic grants from Medical Research Future Fund that do not comprise a conflict, grants from the Victorian Government to mount the Generation Victoria study, grants from the Paul Ramsay Foundation to mount the Generation Victoria study, and grants from the Royal Children's Hospital Foundation to mount the Generation Victoria study outside the submitted work. No other disclosures were reported.

References

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Polygenic Risk Scores and Hearing Loss Phenotypes in Children

Affiliations

Polygenic Risk Scores and Hearing Loss Phenotypes in Children

Authors

Affiliations

Abstract

Conflict of interest statement

References

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