Hearing ability with age in northern European women: a new web-based approach to genetic studies

Abstract

Age-related hearing impairment (ARHI) affects 25-40% of individuals over the age of 65. Despite the high prevalence of this complex trait, ARHI is still poorly understood. We hypothesized that variance in hearing ability with age is largely determined by genetic factors. We collected audiologic data on females of Northern European ancestry and compared different audiogram representations. A web-based speech-to-noise ratio (SNR) hearing test was compared with pure-tone thresholds to see if we could determine accurately hearing ability on people at home and the genetic contribution to each trait compared. Volunteers were recruited from the TwinsUK cohort. Hearing ability was determined using pure-tone audiometry and a web-based hearing test. Different audiogram presentations were compared for age-correlation and reflection of audiogram shape. Using structural equation modelling based on the classical twin model the heritability of ARHI, as measured by the different phenotypes, was estimated and shared variance between the web-based SNR test and pure-tone audiometry determined using bivariate modelling. Pure-tone audiometric data was collected on 1033 older females (age: 41-86). 1970 volunteers (males and females, age: 18-85) participated in the SNR. In the comparison between different ARHI phenotypes the difference between the first two principle components (PC1-PC2) best represented ARHI. The SNR test showed a sensitivity and specificity of 89% and 80%, respectively, in comparison with pure-tone audiogram data. Univariate heritability estimates ranged from 0.70 (95% CI: 0.63-0.76) for (PC1-PC2) to 0.56 (95% CI: 0.48-0.63) for PC2. The genetic correlation of PC1-PC2 and SNR was -0.67 showing that the 2 traits share variances attributed to additive genetic factors. Hearing ability showed considerable heritability in our sample. We have shown that the SNR test provides a useful surrogate marker of hearing. This will enable a much larger sample to be collected at a fraction of the cost, facilitating future genetic association studies.

Figure 1. Receiver operating curve for SNR in comparison to PTA>40 dB.

The receiver operating curve plots the specificity versus the sensitivity of the Speech-to-noise ratio in comparison to hearing ability measured by the pure-tone average >40 dB.

Figure 2. Receiver operating curve of SNR in comparison to PC1–PC2>3.4.

The receiver operating curve plots the specificity versus the sensitivity of the Speech-to-noise ratio in comparison to hearing ability measured by a (PC1–PC2) >3.4.

Figure 3. Results of bivariate variance component modelling.

Graphical presentation of bivariate variance modelling results for PC1–PC2 &SNR (Panel A) and PTA & SNR (Panel B). Univariate heritability (A) and unique environmental factor (E) estimates are given separately for each trait. Correlation between these factors are given by r(a²) and r(e²), respectively.