Callegaro Andrea, Uh Hae-Won, Helmer Quinta, Houwing-Duistermaat Jeanine J
Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands Medical Center, PO Box 9600, 2300RC Leiden, The Netherlands.
BMC Proc. 2009 Dec 15;3 Suppl 7(Suppl 7):S97. doi: 10.1186/1753-6561-3-s7-s97.
Our aim is to develop methods for mapping genes related to age at onset in general pedigrees. We propose two score tests, one derived from a gamma frailty model with pairwise likelihood and one derived from a log-normal frailty model with approximated likelihood around the null random effect. The score statistics are weighted nonparametric linkage statistics, with weights depending on the age at onset. These tests are correct under the null hypothesis irrespective of the weight used. They are simple, robust, computationally fast, and can be applied to large, complex pedigrees. We apply these methods to simulated data and to the Genetic Analysis Workshop 16 Framingham Heart Study data set. We investigate the time to the first of three events: hard coronary heart disease, diabetes, or death from any cause. We use a two-step procedure. In the first step, we estimate the population parameters under the null hypothesis of no linkage. In the second step, we apply the score tests, using the population parameters estimated in the first step.
我们的目标是开发在一般家系中定位与发病年龄相关基因的方法。我们提出了两种计分检验方法，一种源自具有成对似然性的伽马脆弱模型，另一种源自围绕零随机效应具有近似似然性的对数正态脆弱模型。计分统计量是加权非参数连锁统计量，权重取决于发病年龄。在原假设下，无论使用何种权重，这些检验都是正确的。它们简单、稳健、计算速度快，并且可应用于大型复杂家系。我们将这些方法应用于模拟数据以及遗传分析研讨会16弗明汉心脏研究数据集。我们研究了三个事件中第一个事件发生的时间：严重冠心病、糖尿病或任何原因导致的死亡。我们采用两步法。第一步，在无连锁的原假设下估计总体参数。第二步，使用第一步中估计的总体参数应用计分检验。
