PRESBYCUSIS--BIOMEDICAL RISK FACTORS

老年性耳聋——与年龄有关的听力损失——是一种越来越常见的沟通障碍，由于我们社会的老龄化和噪音。老年性痴呆的患病率和严重程度在相同年龄和性别的人群中有很大差异，但这种差异的来源尚不完全清楚。这种可变性的一个主要假定因素是遗传。本研究将继续对老年性痴呆的研究，采用综合检查方法确定老年性痴呆与流行病学和生物医学危险因素的遗传关系。我们建议：a)完成Framingham后代组目标成员的听觉测试，以确定老年性痴呆的患病率（与其父母一样）；b)描述两组的临床老年性痴呆表型；c)利用已有的Genescan数据库对老年性痴呆家系进行定量连锁分析；d)对老年性痴呆家系进行复杂分离分析，评估孟德尔遗传模式；e)识别有遗传遗传的家庭中的危险因素。这是第一个评估老年性痴呆遗传性的现代人类研究。使用最先进的听觉测试和遗传流行病学方法。这项研究只能在像弗雷明汉心脏研究这样的大型亲子组中进行。由于父母的听力测试已经完成，并且大约2/3的目标后代将在当前资金下进行测试，因此该项目的完成将需要在后代研究7的第一部分对剩余的目标后代进行测试。听觉测试不变：纯音阈值、阻抗测听、声阻抗和反射、耳声发射、安静环境下的单词识别、二分数字测试和同侧竞争信息合成句识别。老年性耳聋将按以下方式进行编码：a)按年龄调整的耳聋严重程度；B)临床模式和表型，c)是否为早发型。基因扫描数据库中的定量连锁分析将检查老年性痴呆大家族的DNA。将对不同的表型进行分离分析，这些表型定义为：a)老年性耳聋的严重程度，b)老年性耳聋的模式，c)早发性老年性耳聋，以及d)包括已知风险因素（性别、噪音暴露和心血管疾病）的协变量调整模型。通过严重程度、发病年龄和临床亚型来确定老年性痴呆的特征将有助于确定遗传易感个体中与遗传性老年性痴呆相关的特定危险因素。对遗传性老年性痴呆家族的鉴定将促进未来分子遗传学研究，以确定遗传缺陷的基因。

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.