NEW YORK – New research suggests a polygenic risk score (PRS) developed to gauge hearing loss risk in adulthood can offer clues to hearing loss in childhood, where monogenic hearing loss causes are better known.
"Monogenic causes of childhood hearing loss are well established, as are polygenic risk contributors to age-related hearing loss," co-first and corresponding author Jing Wang, a researcher at the University of Melbourne and the Royal Children's Hospital, and her colleagues wrote in JAMA Otolaryngology-Head & Neck Surgery on Thursday. "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."
To explore that possibility, the investigators brought together hearing audiometry-based hearing measurements and saliva- or blood-based genotyping data for more than 2,000 children enrolled in national and statewide population studies in Australia, looking for potential relationships between childhood hearing traits and a hearing loss PRS developed using hearing loss genome-wide association study summary data for adult UK Biobank participants.
"Compared with children with normal hearing, PRS was associated with elevated odds of clinical subphenotypes of hearing loss in children, including different degrees of severity, laterality, and types of hearing loss," the authors reported, adding that the results "support that PRS is predictive of hearing loss in childhood."
In particular, the team set the PRS score against hearing outcomes in children with or without bilateral or unilateral hearing loss, including 1,488 children between the ages of 11 and 12 years old who took part in the Child Health CheckPoint study and 527 children ranging in age from infancy to the age of 13 from the Victorian Childhood Hearing Longitudinal Databank (VicCHILD).
Indeed, the investigators found that incremental upticks in PRS classifications coincided in increased risk of unilateral or bilateral hearing loss, particularly at the moderate or severe ends of the hearing loss spectrum. Likewise, they noted that the risk of range of hearing loss types — from sensorineural or conductive hearing loss to atresia or auditory neuropathy — were linked to children's scores on the adult PRS.
Together, the authors reported, the new findings "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 … develop hearing loss."
Nevertheless, they noted that the current study relied on polygenic hearing loss contributors established from studies on adult participants and called for future studies focused on genetic risk factors that are specifically found in children with a range of hearing loss symptoms, severity, and subtypes.
"Large-scale studies with objectively defined hearing phenotypes are crucial for refining PRS," the authors wrote, "and have the potential to inform and optimize prediction models for identifying children at high risk of hearing loss."