Longitudinal study of the impact on hearing from aging, genetic background and environmental exposures in male twins

Sammanfattning: Background: Hearing loss is a process that normally develops over many years, and the ability to hear high–frequency sounds is often reduced first. Age, repeated exposure to loud noise and other risk factors, diseases, medications and injury, can damage the various structures of the ear and interfere with hearing. High–frequency hearing loss is common in age–related hearing loss (ARHL) as well as in noise–induced hearing loss (NIHL). It is known that genetic and environmental factors are contributing to the phenotypic development of the hearing impairment, but the heritability of ARHL, NIHL, and tinnitus are poorly understood. Hearing impairment and/or tinnitus is assumed to be caused by multiple genes, however, no candidate gene has been found to be associated with these conditions. Environmental factors of different kinds also influence the degree of hearing loss and the combined effects of genetic and environmental influences on hearing loss are still not fully understood. This thesis aims to investigate the association between genetic and environmental influences on hearing loss and tinnitus. Twin data give a unique opportunity to explore these effects. Methods: The study population was comprised of all male twins in Stockholm and Uppsala counties in 1990, aged 34–79 years at time point 1 (N = 1114) and aged 52–95 years at time point 2 (N = 583), approximately 18 years later. Clinical audiometric evaluation as well as an extensive questionnaire together with genetic analyses based on structural equation models were used to investigate the prevalence of hearing loss and the relative influence of genetic factors on ARHL (Paper I) with bivariate Cholesky decomposition for longitudinal analysis. The prevalence, incidence proportion and heritability of tinnitus were investigated using self–reported tinnitus complaints with co–twin analyses (Paper II). To investigate the environmental influence of hearing in this twin cohort, noise and solvents exposure were assessed, using the extensive questionnaire about work experience over the lifetime that were transferred to occupational work codes, and time at each job and used together with an evaluated Job–Exposure Matrix (Paper III). In all three papers the longitudinal approach of the study made it possible to investigate the hearing loss and tinnitus at two time points and to follow the hearing deterioration over time. Results: Age was an important factor for both hearing loss (especially at high frequencies) and tinnitus prevalence. Increased prevalence of hearing loss ( ≥ 25 dB) was seen over time. The high–frequency hearing loss (HPTA4: average of 3000, 4000, 6000, and 8000 Hz), was most affected. In the younger part of the cohort (below 66.4 age at time point 2) the prevalence of hearing loss was 69% while the older group reached a 94% prevalence at time point 2. The 18–year longitudinal hearing threshold shift, was also more pronounced for the higher frequencies, and the highest rate of change in HPTA4 was 1.3 dB per year for the oldest participants and 1 dB per year for the youngest participants. The relative genetic influences were moderate (53%–65%) for hearing loss especially at lower frequencies (PTA4: average of 500, 1000, 2000, and 4000 Hz), and were of equal magnitude at both time points. Environmental influences were of substantial importance (55%–88%) for the change of hearing i.e. the hearing threshold shift over an 18–year follow–up period (Paper I). The overall prevalence of tinnitus was 13.5% at time point 1 and 33.5% at time point 2. The overall incidence proportion was 27.8%. New tinnitus cases over an 18–year follow–up period had the greatest hearing threshold shift at the higher frequencies. The relative proportion of additive genetic factors for tinnitus was 0.40 at both time point, and the influence of individual–specific environment was 0.56 to 0.61 (Paper II). Occupational noise exposure over the life span affected hearing at all frequencies and also exposure to occupational noise at levels between 75–85 dBA were a significant risk for hearing loss. Impulse noise in the form of firearm use at leisure times was a statistically significant risk factor for hearing loss and tinnitus at all times. Participants with pre–existing hearing loss at time point 1 had a higher threshold shift over the 18–year follow–up period (Paper III). Conclusions: Both hearing loss and tinnitus increase with age. Genetic factors are important for hearing thresholds, but individual–specific environmental factors are more important for hearing threshold shift i.e. the rate of change for hearing over the 18–year follow–up period. A moderate genetic influence (40%) for tinnitus was shown. Pre–existing hearing loss can increase the risk of hearing impairment due to occupational noise exposure. Even low noise exposures below the current threshold limit value of 85 dBA can be a risk for noise–induced hearing loss.