The additive genetic gamma frailty model for linkage analysis of age-of-onset variation.
The additive genetic gamma frailty model for linkage analysis of age-of-onset variation.
复制标题
用于发病年龄变异连锁分析的加性遗传伽马脆弱模型。
DOI：
10.1046/j.1469-1809.1999.6350455.x
复制
发表时间：
1999
影响因子：
1.9
通讯作者：
Li,H
中科院分区：
文献类型：
--
作者：
Li,H
发病年龄是许多复杂疾病连锁分析的关键因素。目前的非参数关联分析方法主要集中在受影响的亲属对或受影响的家庭成员身上，通过指定责任类别的年龄相关外显率来忽略或考虑发病年龄信息。另一方面，伽马脆弱性模型在生物统计学文献中被开发出来，用来模拟发病年龄的家族聚集性。然而，这些脆弱性模型不能直接用于联动分析。本文通过引入遗传向量信息，扩展了伽玛脆弱性模型，并提供了一种半参数化的检测方法。对于假定的疾病位点上的给定遗传向量，我们为核心家庭中的每个个体构建了一个加性遗传γ脆弱性，并使用Cox比例风险模型来模拟发病年龄。我们推导了sib对的条件风险比参数，并在模型下定义了基于似然比的LOD评分统计量。EM算法用于估计参数和最大似然函数。模拟数据集用来说明这些新的统计方法。
Age of onset is a key factor in the linkage analysis of many complex diseases. Current methods in nonparametric linkage analysis are mainly concentrated on the affected relative pairs or affected family members with age of onset information either ignored or taken into account by specifying age-dependent penetrances for liability classes. On the other hand, gamma frailty models were developed in the biostatistics literature to model familial aggregation of age of onset. However, these frailty models cannot be used directly for linkage analysis. This paper extends the gamma frailty model by incorporating inheritance vector information and provides a semiparametric approach for linkage testing. For a given inheritance vector at the putative disease locus, we construct an additive genetic gamma frailty for each individual within a nuclear family and use the Cox proportional hazard model to model age of onset. We derive the conditional hazard ratio parameter for sib pairs and define a likelihood ratio based LOD score statistic under our model. The EM algorithm is used for estimating the parameters and the maximum likelihood functions. Simulated data sets are used to illustrate these new statistical methods.