Presbycusis - age-related hearing loss - is an increasingly common communication disorder due to the aging and noisiness of our society.The prevalence and severity of presbycusis vary substantially in people of the same age and gender but the source(s) of this variability are incompletely understood. A major putative factor for this variability is heredity. The proposed research will continue our study of presbycusis using comprehensive examination methods to determine the inheritability of presbycusis in relation to its epidemiology and biomedical risk factors. We propose to: a) finish the auditory testing of the targeted members of the Framingham Offspring Group to determine the prevalence of presbycusis (as for their parents; b) delineate clinical presbycusis phenotypes in both groups; c) perform quantitative linkage analysis using the existing Genescan data base for the families with presbycusis pedigrees, d) perform complex segregation analysis of presbycusic families to assess the Mendelian inheritance patterns; and e) identity risk factors in families with genetic transmission. This is the first modern human study to assess the heritability of presbycusis. State-of-the-art methodology for auditory testing and genetic epidemiology are used. This research can only be done in a large parent-offspring group such as the Framingham Heart Study. Because the parents' hearing testing is done, and about 2/3 of the target Offspring will have been tested under the current funding, completion of this project will require testing of the remaining target Offspring during the first part of Offspring Study 7. Auditory tests are unchanged: pure-tone thresholds, immittance audiometry, acoustic impedance and reflectance, otoacoustic emissions, word recognition in quiet, Dichotic Digits test and the Synthetic Sentence Identification with Ipsilateral Competing Message. Presbycusis will be coded by: a) age-adjusted severity of loss; b) clinical pattern and phenotype, and c) whether it is of an early-onset type or not. Quantitative linkage analysis in the Genescan data base will examine the DNA of large families with presbycusis. Segregation analysis will be done for different phenotypes defined as: a) severity of presbycusis, b) presbycusis pattern, c) early-onset presbycusis, and d) co-variate adjusted models that will include known risk factors (gender, noise exposure, and cardiovascular diseases). Characterizing presbycusis by severity, age of onset, and clinical subtype will help to identify specific risk factors associated with hereditary presbycusis among genetically predisposed individuals. Identification of families with inherited presbycusis will facilitate future molecular genetic studies to identify genes for inherited defects.
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