Genetic Associations in Age-Related Hearing Thresholds

Abstract

Objective: To determine the inheritance of age-related hearing loss.Design: Cohort study comparing aggregation of hearing levels in genetically unrelated people (spouse pairs) and in genetically related people (sibling pairs, parentchild pairs).Setting: Framingham Heart Study biennial Examination 15 (1973) and Framingham Offspring Study Examination 6 (1995-1998. Main Outcome Measures: Audiometric pure-tone thresholds at 250 to 8000 Hz were obtained and puretone average (PTA) hearing thresholds were calculated for the middle (0.5-2 kHz), high (4-8 kHz), and low (0.25-1 kHz) frequencies for each ear. The shape of the audiogram was categorized as either normal, abrupt highfrequency loss (sensory phenotype) or flat loss (strial phenotype). Correlations were made using the Familial Correlations program of the Statistical Analysis for Genetic Epidemiology software system. The level of significance was P = .01.Results: Hearing threshold levels did not aggregate in spouses. Significant aggregation was noted in siblings and parent-child pairings for PTA at low, middle, and high frequencies. Sisters but not brothers had significant aggregation of each PTA measure. Mother-daughter and mother-son pairs but not father-son pairs had significant aggregation of hearing levels. For the sensory phenotype, there was significant aggregation in all related pairs except for father-child pairs. For the strial phenotype, there was significant aggregation of hearing levels in the related female pairs but not in the related male pairs. Conclusions:A clear familial aggregation occurs for agerelated hearing levels, sensory presbycusis phenotypes, and strial presbycusis phenotypes. The aggregations are stronger in women than in men. The heritability estimate was greater for the strial phenotypes than for the sensory phenotypes. The data support a genetic effect on the inheritance of presbycusis in women and a mixed, genetically acquired cause in men.

Ageing and hearing loss

“…Presbycusis does cluster in families [35] and heritability estimates indicate that 35-55% of the variance of ARHL is attributable to the effects of genes: A Swedish study consisting of 250 monozygotic and 307 dizygotic male twins (aged 36-80) showed a heritability of 47% for the population above 65, using both questionnaire and audiometric data [36]. Using the same analytical method, the National Academy of Science-National Research Council (NAS-NRC) ageing twin panel study in the USA has estimated the heritability at 61% [37].…”

“…Across all ages, environmental and hereditary factors were found to be important sources of variation, with environmental factors becoming more influential with increasing age. In the Framingham cohort, heritability of presbycusis phenotypes was estimated to be 0.35-0.55, based on evaluations of audiometric examinations in the Framingham cohort [35]. The study compared the auditory status in genetically unrelated (spouse pairs) and genetically related people (sibling pairs, parent-child pairs), revealing a clear familial aggregation for agerelated hearing levels.…”

A genome-wide association study for age-related hearing impairment in the Saami

“…1,2 The involvement of genetic factors in the development of this multifactorial disorder was demonstrated by several heritability studies. [3][4][5] Only recently have the first studies aiming at the identification of these genetic factors been conducted. Hitherto, three linkage studies have been performed, [6][7][8] but only one region on chromosome 8q24.13-q24.22 reached genomewide significance.…”

Is DFNA5 a susceptibility gene for age-related hearing impairment?

“…The subjects were grouped by type of ARHI; within each type, increasing number indicates poorer hearing. 3 Of the Framingham Heart Study subjects with hearing data there were 1789 individuals that were members of 328 pedigrees used for linkage analysis in the DFNA5 region. Additionally, 93 unrelated individuals with hearing loss (type 1, 2 or 3 in both ears) and 83 unrelated individuals with normal hearing (type 0 in both ears) were selected for association studies.…”

“…The heritability estimates of this study suggested that 35 -55% of the variance of sensory ARHI is attributable to the effects of genes. 3 Up to now, nothing is known about the nature of the genes that contribute to ARHI. As the most frequent type of ARHI is progressive, sensorineural and most pronounced in the high frequencies, genes causing monogenic hearing impairment with phenotypic similarities to ARHI (although with a much younger age-at-onset) are excellent candidate ARHI susceptibility genes.…”