PRESBYCUSIS--BIOMEDICAL RISK FACTORS

由于老年人数量的增加，老年性耳聋越来越常见。 我们的社会。老年性耳聋的患病率和严重程度差别很大。 在相同年龄和性别的人中，但这种差异的来源(S) 目前还没有得到澄清。一个主要的、未经检验的因素是遗传。这个 拟议的项目将继续通过使用新的 老年性耳聋的检查方法及遗传度测定 与其流行病学和生物医学危险因素的关系。我们会估计 老年性耳聋在多大程度上是由基因决定的，在多大程度上是由基因决定的 结果是后天的侮辱，包括内在的和外在的。 我们建议：a)进行一系列听觉测试，以确定 弗雷明翰后代组(AS)成员中老年性耳聋的患病率 已经为他们的父母参加了Framingham Cohort Group)； B)描述临床老年性耳聋的亚型(即对应于 感觉、工业、神经和耳蜗神经传导类型) 两组；c)老年性耳聋的复杂分离分析 评估老年性耳聋的孟德尔遗传模式；以及 D)确定遗传传播家庭中的风险因素。这将是 是第一个记录老年性耳聋遗传性的人类研究，以及 将采用最先进的方法进行听觉测试和基因 流行病学。这项研究只能在体型较大的亲子之间进行 像弗雷明翰研究这样的小组。因为父母的听力测试 已经完成，这个项目的完成将只需要测试 他们的孩子在弗雷明翰后代的第六个考试周期中 学习。 建议的听力测试有：纯音听阈值、导纳测听、 声阻抗和反射，耳声发射，世界 在安静和两个中枢听觉测试中的识别，双指测验， 同侧竞争信息下的合成句子识别。 听力和听觉功能的多项测量是必要的 确定老年性耳聋的亚型。老年性耳聋将由a)严重程度编码 损失；b)是否为早发型；c)临床亚型。 心血管和一般健康状况数据将作为以下内容的一部分 弗雷明翰后代研究，由NAT‘l心脏公司的一份合同资助 肺和血液系统。这些数据将用于我们的分析。 将对定义为：a)的不同表型进行分离分析 严重程度，b)早发，c)临床亚型，d)协变量调整 包括已知风险因素的模型(性别、噪声暴露和 心血管疾病)。通过根据严重程度、年龄来描述老年性耳聋 发病时间和临床亚型我们希望确定特定的危险因素 与遗传性老年性耳聋相关的遗传易感性 个人。遗传性老年性耳聋家系的鉴定将 促进未来的连锁研究和分子遗传学研究，这可以 重点是识别导致遗传缺陷的基因。

Presbycusis is increasingly common due to the growing number of elderly in 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 have not been elucidated. A major, unexamined factor is heredity. The proposed projects will continue the study of presbycusis by using new examination methods and by determining the heritability of presbycusis in relation to its epidemiology and biomedical risk factors. We will estimate to what extent presbycusis is genetically determined and to what extent it results from acquired insults, both intrinsic and extrinsic. We propose to: a) perform a battery of auditory tests to determine the prevalence of presbycusis in members of the Framingham Offspring Group (as has been done for their parents enrolled in the Framingham Cohort Group); b) delineate clinical presbycusis subtypes (i.e. corresponding to the sensory, strial, neural, and cochlear conductive types of Schuknecht) in both groups; c) perform complex segregation analysis of presbycusis families to assess the Mendelian inheritance patterns for presbycusis; and d) identify risk factors in families with genetic transmission. This will be the first human study to document the heritability of presbycusis, and will employ state-of-the-art methodology for auditory testing and genetic epidemiology. This research can only be done in a large parent-offspring group such as the Framingham Study. Because hearing testing of the parents has been done, completion of this project will require testing only of their children during the 6th examination cycle of the Framingham Offspring Study. Auditory tests proposed are: pure tone thresholds, immittance audiometry, acoustic impedance and reflectance, otoacoustic emissions, world recognition in quiet and two central auditory tests, Dichotic Digits test, and Synthetic Sentence Identification with Ipsilateral Competing message. Multiple measures of hearing and auditory function are necessary to identify presbycusis subtypes. Presbycusis will be coded by a) severity of loss; b) whether it is an early-onset type; and c) clinical subtype. Cardiovascular and general health status data will be obtained as part of the Framingham Offspring Study, funded by a contract from the Nat'L. Heart Lung and Blood Inst. These data will be available for our analyses. Segregation analysis will be done for different phenotypes defined as; a) severity, b) early-onset, c) clinical subtype, and d) co-variate adjusted models including known risk factors (gender, noise exposure, and cardiovascular diseases). By characterizing presbycusis by severity, age of onset, and clinical subtype we hope to identify specific risk factors associated with hereditary presbycusis among genetically predisposed individuals. Identification of families with inherited presbycusis will facilitate future linkage studies and molecular genetic studies which can focus on the identification of genes responsible for inherited defects.