Fransen Erik, Van Laer Lut, Lemkens Nele, Caethoven Goele, Flothmann Kris, Govaerts Paul, Van de Heyning Paul, Van Camp Guy
Department of Medical Genetics, University of Antwerp, Belgium.
Ear Hear. 2004 Apr;25(2):133-41. doi: 10.1097/01.aud.0000120362.69077.0b.
Approximately half of the variance of Age-Related Hearing Impairment (ARHI) is attributable to environmental risk factors, and the other half to genetic factors. None of these genes has ever been identified, but the genes involved in monogenic nonsyndromic hearing impairment are good candidates. Here we define and validate a quantitative trait value for ARHI, correcting for age and gender, to allow the genetic study of ARHI as a quantitative trait.
Based on the ISO 7029 standard, we convert audiometric data into a Z-score, an age- and gender-independent value expressing to what extent a person is affected by ARHI. The validity of this approach is checked using a test population of randomly collected subjects. The power to evaluate the contribution of a candidate gene to ARHI is assessed using simulated populations. As an example, one ARHI candidate gene is analyzed.
In our test population, Z-scores were normally distributed although the mean did not equal zero. Z-scores were independent of age, and there was no difference between men and women. Power studies using simulated populations indicated that to detect moderate genetic effects, sample sizes of at least 500 random subjects are necessary.
The Z-score conversion appears to be a valid method to describe to what extent a subject is affected by ARHI, allowing to compare persons from different age and gender. This method can be the basis of future, powerful studies to identify ARHI genes.
年龄相关性听力减退（ARHI）约一半的变异归因于环境危险因素，另一半归因于遗传因素。这些基因均未被鉴定出来，但参与单基因非综合征性听力减退的基因是很好的候选基因。在此，我们定义并验证了ARHI的一个定量性状值，对年龄和性别进行了校正，以便将ARHI作为一个定量性状进行遗传学研究。
基于ISO 7029标准，我们将听力测定数据转换为Z分数，这是一个与年龄和性别无关的值，可表达一个人受ARHI影响的程度。使用随机收集的受试者测试群体来检验这种方法的有效性。使用模拟群体评估评估候选基因对ARHI贡献的效能。作为一个例子，分析了一个ARHI候选基因。
在我们的测试群体中，Z分数呈正态分布，尽管均值不等于零。Z分数与年龄无关，男性和女性之间没有差异。使用模拟群体进行的效能研究表明，要检测中等程度的遗传效应，至少需要500名随机受试者的样本量。
Z分数转换似乎是一种有效的方法，可描述受试者受ARHI影响的程度，从而能够比较不同年龄和性别的个体。这种方法可作为未来强大的ARHI基因鉴定研究的基础。
