medwireNews: A polygenic risk score (PRS) developed for self-reported hearing difficulty in adults is associated with a wide range of childhood hearing loss phenotypes, Australian study findings indicate.
Jing Wang (Murdoch Children’s Research Institute, Parkville, Victoria) and co-investigators say their research “could partly explain the variability in hearing phenotypes from the same monogenetic variant and why some children, but not others, exposed to the same environment (eg, pre-term birth) develop hearing loss.”
They explain that “[m]ore than 200 genes have been identified associated with monogenic hearing loss at birth,” but it is unclear whether polygenic risk also contributes to childhood hearing loss.
To investigate, Wang and team applied a PRS, based on 23,000 genetic variants and developed using UK Biobank genome-wide association study results for self-reported hearing difficulty in adults, to two population-based cohorts of children in Australia whose hearing ability ranged from normal through all levels of hearing loss.
This included 1488 participants (aged 11–12 years, 49.8% boys) of the Child Health CheckPoint, a population-based, cross-sectional study nested within the Longitudinal Study of Australian Children, and 527 individuals (aged 0–13 years, 55.2% boys) from the Victorian Childhood Hearing Longitudinal Databank (VicCHILD), a statewide population-based registry open to every child with congenital hearing loss in Victoria, Australia.
All the children had genotype data generated from saliva- or blood-derived DNA using global single nucleotide variant arrays.
The researchers report in JAMA Otolaryngology Head & Neck Surgery that each standard deviation (SD) increase in PRS was associated with significant 1.3-, 5.1-, and 5.3-fold increased odds of mild, moderate, and severe or worse unilateral hearing loss, respectively, compared with normal hearing.
Similarly, the odds of mild, moderate, and severe or worse bilateral hearing loss versus normal hearing increased significantly by a corresponding 3.9-, 6.6-, and 6.4-fold with each SD increase in PRS.
When separating by types of hearing loss, each SD increment in PRS increased the odds of sensorineural, conductive, mixed, auditory neuropathy, and atresia, by a significant 8.5-, 8.5-, 9.0-, 8.8-, and 10.6-fold, respectively, compared with normal hearing.
Wang et al say that their study is the first to comprehensively assess the role of polygenic inheritance in hearing loss phenotypes among children.
They believe it indicates “that child hearing loss is polygenic and there might be shared genetic risk or biologic pathways between age-related hearing loss and childhood hearing loss, and between different types of hearing loss.”
The authors conclude: “Large-scale studies with objectively defined hearing phenotypes are crucial for refining PRS and have the potential to inform and optimize prediction models for identifying children at high risk of hearing loss.”
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JAMA Otolaryngol Head Neck Surg 2024; doi:10.1001/jamaoto.2024.3659
