Extensions to sib-pair linkage tests applicable to disorders characterized by delayed onset.
Extensions to sib-pair linkage tests applicable to disorders characterized by delayed onset.
复制标题
同胞对连锁测试的扩展适用于延迟发作的疾病。
DOI：
10.1002/gepi.1370070607
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发表时间：
1990
影响因子：
2.1
通讯作者：
Elston,RC
中科院分区：
文献类型：
--
作者：
Dawson,DV;Kaplan,EB;Elston,RC
Haseman和Elston [Behav Genet 2：3-19，1972]开发的同胞对连锁检验方法的扩展被提出，其中包含了发病年龄和检查年龄的信息。发病年龄校正的替代来源进行了描述，包括与发病年龄分布相关的参数估计模型。模拟被用来检查的方法时，适用于显性疾病的晚发型范围内的重组分数从非常紧密的联系，自由重组的性能。对于每组遗传参数，在一个完整的确定模型下生成了50个四成员亲缘关系的2,000个样本，以研究功效和I型错误，并比较所提出的技术的变体。将有和没有发病年龄校正的结果相互比较，并与完全脱髓鞘时获得的结果进行比较，即，模拟研究的结果表明，当使用发病年龄扩展时，在存在连锁的情况下，显著性概率得到增强。所提出的方法与可接受的水平的I型错误，并获得实质性收益的权力时，发病年龄和年龄在检查的相关数据纳入分析。
Extensions of the approach to sib‐pair linkage tests developed by Haseman and Elston [Behav Genet2:3–19, 1972] are proposed which incorporate information on age of onset and age at examination. Alternate sources for the age of onset corrections are described, including models for the estimation of parameters associated with the age of onset distribution. Simulation is used to examine the performance of the approach when applied to a dominant disorder of late onset for a range of recombination fractions ranging from very tight linkage to free recombination. For each set of genetic parameters, 2,000 samples of 50 four‐member sibships were generated under a complete ascertainment model to investigate power and Type I error, and to compare variants of the proposed technique. Results with and without age‐of‐onset correction are compared to each other and to those obtainable if penetrance were complete, i.e., if there were no intervening age‐of‐onset phenomenon.Results from simulation studies show that significance probabilities are enhanced in the presence of linkage when age‐of‐onset extensions are used. The proposed methods are associated with acceptable levels of Type I error, and substantive gains in power are obtained when data related to age of onset and age at examination are incorporated into the analysis.