Polygenic Risk Scores and Hearing Loss Phenotypes in Children
Jing Wang1,2, Fan He1,3,4, Daisy A Shepherd1,2
1Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.
Insights
A polygenic risk score (PRS) for adult hearing loss is linked to childhood hearing loss across all severities. This genetic factor contributes to understanding hearing variations in children, even with other influences.
Area of Science:
- Genetics
- Otolaryngology
- Pediatrics
Background:
- Monogenic causes of childhood hearing loss are known.
- Polygenic risk scores (PRS) are established contributors to age-related hearing loss.
- The role of PRS in childhood hearing loss remains largely unexplored.
Purpose of the Study:
- To investigate the association between a PRS for adult hearing loss and various childhood hearing loss phenotypes.
- To determine if PRS contributes to the spectrum of childhood hearing loss, from normal to profound.
Main Methods:
- Utilized a cross-sectional study design combining two Australian population cohorts: Child Health CheckPoint and VicCHILD.
- Generated genotype data from DNA samples.
- Calculated PRS based on UK Biobank GWAS data for adult hearing difficulty; analyzed associations with childhood hearing outcomes (laterality, severity, type) using multinominal logistic regressions.
Main Results:
- A 1-SD increase in PRS was significantly associated with higher odds of unilateral hearing loss across all severity levels (mild, moderate, severe or worse).
- The PRS was also linked to increased odds of bilateral hearing loss and all hearing loss types.
- The PRS explained a portion of the variation in hearing phenotypes, even when considering shared genetic and environmental factors like preterm birth.
Conclusions:
- A PRS developed for adult hearing difficulty is associated with a broad range of childhood hearing loss phenotypes.
- PRS may contribute to the variability observed in childhood hearing loss, independent of or in conjunction with other factors.
- Further large-scale studies with objective hearing assessments are needed to refine PRS and identify children at high risk for hearing loss.
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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