PRESBYCUSIS--BIOMEDICAL RISK FACTORS

老年性耳聋--与年龄相关的听力损失--是由于我们的社会老龄化和噪音造成的一种日益常见的沟通障碍。在相同年龄和性别的人群中，老年性耳聋的患病率和严重程度存在很大差异，但这种差异的来源(S)尚不完全清楚。这种变异的一个主要推定因素是遗传。这项拟议的研究将继续我们对老年性耳聋的研究，使用全面的检查方法来确定老年性耳聋的遗传性与其流行病学和生物医学危险因素的关系。我们建议：a)完成Framingham后代组目标成员的听力测试，以确定老年性耳聋的患病率(与他们的父母一样)；b)描述两组中的临床老年性耳聋表型；c)使用现有的Genescan数据库对老年性耳聋家系进行定量连锁分析；d)对老年性耳聋家系进行复杂的分离分析，以评估孟德尔遗传模式；以及e)在具有遗传遗传的家庭中识别危险因素。这是第一项评估老年性耳聋遗传性的现代人类研究。使用了最先进的听觉测试和遗传流行病学方法。这项研究只能在一个大的亲子群体中进行，比如弗雷明翰心脏研究。由于父母的听力测试已经完成，在目前的资助下，大约2/3的目标子女将进行测试，完成这个项目将需要在子女研究7的第一部分期间对剩余的目标子女进行测试。听觉测试保持不变：纯音阈值、导纳测听、声阻抗和反射、耳声发射、安静中的单词识别、双音数字测试和具有同侧竞争信息的合成句子识别。老年性耳聋的编码标准是：a)年龄调整后的耳聋严重程度；b)临床类型和表型；c)是否为早发性耳聋。Genescan数据库中的定量连锁分析将检查患有老年性耳聋的大家族的DNA。将对不同的表型进行分离分析，定义为：a)老年性耳聋的严重程度，b)老年性耳聋的类型，c)早发性老年性耳聋，以及d)将包括已知危险因素(性别、噪声暴露和心血管疾病)的协变量调整模型。根据严重程度、发病年龄和临床亚型确定老年性耳聋的特征将有助于在遗传易感性个体中识别与遗传性老年性耳聋相关的特定危险因素。遗传性老年性耳聋家系的鉴定将有助于未来的分子遗传学研究，以确定遗传性缺陷的基因。

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.