PRESBYCUSIS--BIOMEDICAL RISK FACTORS

老年性耳聋是越来越普遍，由于越来越多的老年人， 我们的社会 老年性耳聋的患病率和严重程度差异很大 在相同年龄和性别的人中，但这种变异性的来源 还没有被阐明。 一个主要的、未经检验的因素是遗传。 的 拟议的项目将继续研究老年性耳聋， 检查方法和通过测定老年性耳聋的遗传度， 与其流行病学和生物医学风险因素有关。 我们估计 老年性耳聋在多大程度上是由基因决定的， 结果来自后天的伤害，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 老年性耳聋的患病率在成员的Fragmentary后代组（作为 已经为他们的父母参加了Fraidian队列组）; B）描绘临床老年性耳聋亚型（即对应于 Schuknecht的感觉、听觉、神经和耳蜗传导类型）， 两组; c）进行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）查明有遗传传播的家庭中的危险因素。 这将 成为第一个记录老年性耳聋遗传性的人类研究， 将采用最先进的方法进行听觉测试和遗传学研究， 流行病学 这项研究只能在一个大型的亲子 比如说，Fraud Study。 因为对父母的听力测试 已经完成，完成该项目将只需要测试 在第六轮考试期间， Study. 建议的听觉测试有：纯音听阈，导抗测听， 声阻抗和反射率，耳声发射，世界 在安静和两个中央听觉测试中的识别，双耳分音数字测试， 和具有同侧竞争信息的合成句识别。 听力和听觉功能的多项措施是必要的， 识别老年性耳聋亚型。 老年性耳聋将按照a）严重程度编码 损失; B）是否为早发型;和c）临床亚型。 心血管和一般健康状况数据将作为 由美国国家自然科学基金会的一份合同资助的Framelo后代研究。心脏 肺部和血液研究所。这些数据将可用于我们的分析。 将对定义为以下的不同表型进行分离分析：a） 严重程度，B）早发性，c）临床亚型，d）协变量校正 模型包括已知的风险因素（性别，噪音暴露， 心血管疾病）。 通过按严重程度、年龄 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人群 个体 遗传性老年性聋家系的鉴定 促进未来的连锁研究和分子遗传学研究， 专注于鉴定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.