Association of Polygenic Risk Scores for Hearing Difficulty in Older Adults With Hearing Loss in Mid-Childhood and Midlife

Abstract

Although more than 200 genes have been associated with monogenic congenital hearing loss, the polygenic contribution to hearing decline across the life course remains largely unknown. To examine the association of polygenic risk scores (PRSs) for self-reported hearing difficulty among adults (40-69 years) with measured hearing and speech reception abilities in mid-childhood and early midlife. This was a population-based cross-sectional study nested within the Longitudinal Study of Australian Children that included 1608 children and 1642 adults. Pure tone audiometry, speech reception threshold against noise, and genetic data were evaluated. Linear and logistic regressions of PRSs were conducted for hearing outcomes. Study analysis was performed from March 1 to 31, 2022. Genotypes were generated from saliva or blood using global single-nucleotide polymorphisms array and PRSs derived from published genome-wide association studies of self-reported hearing difficulty (PRS1) and hearing aid use (PRS2). Hearing outcomes were continuous using the high Fletcher index (mean hearing threshold, 1, 2, and 4 kHz) and speech reception threshold (SRT); and dichotomized for bilateral hearing loss of more than 15 dB HL and abnormal SRT. Included in the study were 1608 children (mean [SD] age, 11.5 [0.5] years; 812 [50.5%] male children; 1365 [84.9%] European and 243[15.1%] non-European) and 1642 adults (mean [SD] age, 43.7 [5.1] years; 1442 [87.8%] female adults; 1430 [87.1%] European and 212 [12.9%] non-European individuals). In adults, both PRS1 and PRS2 were associated with hearing thresholds. For each SD increment in PRS1 and PRS2, hearing thresholds were 0.4 (95% CI, 0-0.8) decibel hearing level (dB HL) and 0.9 (95% CI, 0.5-1.2) dB HL higher on the high Fletcher index, respectively. Each SD increment in PRS increased the odds of adult hearing loss of more than 15 dB HL by 10% to 30% (OR for PRS1, 1.1; 95% CI, 1.0-1.3; OR for PRS2, 1.3; 95% CI, 1.1-1.5). Similar but attenuated patterns were noted in children (OR for PRS1, 1.1; 95% CI, 0.8-1.2; OR for PRS2, 1.2; 95% CI, 1.0-1.5). Both PRSs showed minimal evidence of associations with speech reception thresholds or abnormal SRT in children or adults. This population-based cross-sectional study of PRSs for self-reported hearing difficulty among adults found an association with hearing ability in mid-childhood. This adds to the evidence that age-related hearing loss begins as early as the first decade of life and that polygenic inheritance may play a role together with other environmental risk factors.