Dataset Information

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

ABSTRACT:

Background

Age-related hearing loss is a common, heterogeneous disease with a strong genetic component. More than 100 loci have been reported to be involved in human hearing impairment to date, but most of the genes underlying human adult-onset hearing loss remain unknown. Most genetic studies have focussed on very rare variants (such as family studies and patient cohort screens) or very common variants (genome-wide association studies). However, the contribution of variants present in the human population at intermediate frequencies is hard to quantify using these methods, and as a result, the landscape of variation associated with adult-onset hearing loss remains largely unknown.

Results

Here we present a study based on exome sequencing and self-reported hearing difficulty in the UK Biobank, a large-scale biomedical database. We have carried out variant load analyses using different minor allele frequency and impact filters, and compared the resulting gene lists to a manually curated list of nearly 700 genes known to be involved in hearing in humans and/or mice. An allele frequency cutoff of 0.1, combined with a high predicted variant impact, was found to be the most effective filter setting for our analysis. We also found that separating the participants by sex produced markedly different gene lists. The gene lists obtained were investigated using gene ontology annotation, functional prioritisation and expression analysis, and this identified good candidates for further study.

Conclusions

Our results suggest that relatively common as well as rare variants with a high predicted impact contribute to age-related hearing impairment and that the genetic contributions to adult hearing difficulty may differ between the sexes. Our manually curated list of deafness genes is a useful resource for candidate gene prioritisation in hearing loss.

SUBMITTER: Lewis MA

PROVIDER: S-EPMC9238072 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo evaluate discrepancies prevalent between self-reported hearing difficulty (SHD) and audiometrically measured hearing loss (AHL) and factors associated with such discrepancies.DesignNationwide cross-sectional survey.SettingData from 2010 to 2012 Korea National Health and Nutrition Examination Survey conducted by the Korea Centers for Disease Control and Prevention.ParticipantsWe included 14 345 participants aged ≥19 years who had normal tympanic membranes (mean age of 49 years).MeasuresSelf-reported hearing was assessed by asking participants whether they had difficulty in hearing. AHL was defined as >25 dB of mean hearing thresholds measured at 0.5, 1, 2 and 4 kHz in better ear. Underestimated hearing impairment (HI) was defined as having AHL without SHD. Likewise, overestimated HI was defined as having SHD without AHL. Prevalence of underestimated and overestimated HIs was determined. Univariable and multivariable analyses were performed to examine factors associated with such discrepancies compared with concordant HL.ResultsAmong 14 345 participants, 1876 (13.1%) had underestimated HI while 733 (5.1%) had overestimated HI. Multivariable models revealed that participants who had discrepancies between SHD and AHL were less likely to have older age (OR: 0.979, 95% CI: 0.967 to 0.991 for the underestimated HI, OR: 0.905, 95% CI: 0.890 to 0.921 for the overestimated HI) and tinnitus (OR: 0.425, 95% CI: 0.344 to 0.525 for the underestimated HI and OR 0.523, 95% CI: 0.391 to 0.699 for the overestimated HI) compared with those who had concordant HI. Exposure to occupational noise (OR: 0.566, 95% CI: 0.423 to 0.758) was associated with underestimated HI, and medical history of hypertension (OR: 1.501, 95% CI: 1.061 to 2.123) and depression (OR: 1.771, 95% CI: 1.041 to 3.016) was associated with overestimated HI.ConclusionAge, tinnitus, occupational noise exposure, hypertension and depression should be incorporated into evaluation of hearing loss in clinical practice.