Genetic associations in age-related hearing thresholds

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, parent-child pairs). Setting: Framingham Heart Study biennial Examination 15 (1973-1975) and Fra mingham Offspring Study Examination 6 (1995-1998). Subjects: Members of the Framingham cohorts with hearing tests and with a r elative in the Framingham hearing study. Main Outcome Measures: Audiometric pure-tone thresholds at 250 to 8000 Hz w ere obtained and pure-tone average (PTA) hearing thresholds were calculated for the middle (0.5-2 kHz), high (4-8 kHz), and low (0.25-1 kHz) frequenci es for each ear. The shape of the audiogram was categorized as either norma l, abrupt high-frequency loss (sensory phenotype) or flat loss (strial phen otype). Correlations were made using the Familial Correlations program of t he 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 ag gregation of each PTA measure. Mother-daughter and mother-son pairs but not father-son pairs had significant aggregation of hearing levels. For the se nsory phenotype, there was significant aggregation in all related pairs exc ept for father-child pairs. For the strial phenotype, there was significant aggregation of hearing levels in the related female pairs but not in the r elated male pairs. Conclusions: A clear familial aggregation occurs for age-related hearing le vels, sensory presbycusis phenotypes, and strial presbycusis phenotypes. Th e 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 a nd a mixed, genetically acquired cause in men.