Self-reported hearing loss questions provide a good measure for genetic studies: a polygenic risk score analysis from UK Biobank

Abstract

Age-related hearing impairment (ARHI) is very common in older adults and has major impact on quality of life. The heritability of ARHI has been estimated to be around 50%. The present study aimed to estimate heritability and environmental contributions to liability of ARHI and the extent to which a polygenic risk score (PRS) derived from a recent genome-wide association study of questionnaire items regarding hearing loss using the UK Biobank is predictive of hearing loss in other samples. We examined (1) a sample from TwinsUK who have had hearing ability measured by pure-tone audiogram and the speech-to-noise ratio test as well as questionnaire measures that are comparable with the UK Biobank questionnaire items and (2) European and non-European samples from the UK Biobank which were not part of the original GWAS. Results indicated that the questionnaire items were over 50% heritable in TwinsUK and comparable with the objective hearing measures. In addition, we found very high genetic correlation (0.30-0.84) between the questionnaire responses and objective hearing measures in the TwinsUK sample. Finally, PRS computed from weighted UK Biobank GWAS results were predictive of both questionnaire and objective measures of hearing loss in the TwinsUK sample, as well as questionnaire-measured hearing loss in Europeans but not non-European subpopulations. These results demonstrate the utility of questionnaire-based methods in genetic association studies of hearing loss in adults and highlight the differences in genetic predisposition to ARHI by ethnic background.

Sex differences, cross-ancestry generalizability, and noise-smoking interactions in the polygenic architecture of hearing loss in adults

“…These included three questionnaire-derived self-reported hearing traits and one trait derived from audiometric measures. Consistent with previous studies 16,53 , we observed that SRT-derived assessment had a very low SNP-h 2 (<1%) that did not permit us to investigate further this HL outcome. Conversely, self-reported HL outcomes showed significant SNP-h 2 that was informative to investigate their polygenic architecture.…”

“…With respect to STRderived traits, the SNP-h 2 was lower <1% with only right-ear assessment with an estimate statistically different from zero (SRT-right SNP-h 2 = 0.009±0.002; Table 1). The limited informativeness of the SRT test in genetic studies is in line with previous findings 16,53 . Accordingly, the SRT-derived traits were excluded for further evaluations.…”

Investigating the characteristics of genes and variants associated with self-reported hearing difficulty in older adults in the UK Biobank

“…The biggest limitation of this study is the lack of measured hearing impairment (such as an audiogram) and detailed auditory phenotyping. Self-reported hearing difficulty has been shown to be sufficiently informative for general hearing capacity [ 9 , 47 ], but there is more to hearing loss than just an average threshold shift. It is likely that we have missed mild or even moderate hearing loss, and also unilateral hearing loss.…”

Investigating the Characteristics of Genes and Variants Associated with Self-Reported Hearing Difficulty in Older Adults in the UK Biobank

“…The biggest limitation of this study is the lack of measured hearing loss (such as an audiogram) and detailed auditory phenotyping. Self-reported hearing loss has been shown to be sufficiently informative for general hearing capacity [9,76], but there is more to hearing loss than just an average threshold shift. Being able to compare specific subtypes of age-related hearing loss (for example, using a classification system such as the one described in [77], [78], and [79]), offers the potential to link genes with a high variant load to specific inner ear pathologies, an important step for stratifying patient populations and developing therapeutics.…”

“…The biggest limitation of this study is the lack of measured hearing impairment (such as an audiogram) and detailed auditory phenotyping. Self-reported hearing difficulty has been shown to be sufficiently informative for general hearing capacity [9, 52], but there is more to hearing loss than just an average threshold shift. It is likely that we have missed mild or even moderate hearing loss, and also unilateral hearing loss.…”