A full-likelihood method for the evaluation of causality of sequence variants from family data
A full-likelihood method for the evaluation of causality of sequence variants from family data
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DOI：
10.1086/378100
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发表时间：
2003-09-01
影响因子：
9.8
通讯作者：
Goldgar, DE
中科院分区：
文献类型：
--
作者：
Thompson, D;Easton, DF;Goldgar, DE
在许多疾病基因中，由于不确定它们与疾病的关联，检测到的所有罕见变异中的很大一部分还不能用于遗传咨询。对这些未分类变异的特征的一种方法是分析受影响携带者家族中与疾病共分离的模式。Petersen等人。以前提供了一种简单的贝叶斯方法来评估这种序列变体的因果关系。在本报告中，我们提出了一种基于全系谱似然的更一般的方法，并且我们表明，使用该方法可以比以前的方法提供更准确和更信息的因果关系评估。我们进一步表明，重要的是，家系信息尽可能完整，并在未受影响的个体和表型未知的个体之间进行区分。
In many disease genes, a substantial fraction of all rare variants detected cannot yet be used for genetic counselling because of uncertainty about their association with disease. One approach to the characterization of these unclassified variants is the analysis of patterns of cosegregation with disease in affected carrier families. Petersen et al. previously provided a simplistic Bayesian method for evaluation of causality of such sequence variants. In the present report, we propose a more general method based on the full pedigree likelihood, and we show that the use of this method can provide more accurate and informative assessment of causality than could the previous method. We further show that it is important that the pedigree information be as complete as possible and that the distinction be made between unaffected individuals and those of unknown phenotype.