Exploiting gene x gene interaction in linkage analysis.
Exploiting gene x gene interaction in linkage analysis.
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DOI：
10.1186/1753-6561-1-s1-s64
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Vieland VJ
中科院分区：
文献类型：
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作者：
Huang Y;Bartlett CW;Segre AM;O'Connell JR;Mangin L;Vieland VJ
当两个基因相互作用导致临床上重要的表型时，似乎有理由期望我们可以利用其中一个基因座的基因型信息来提高我们检测另一个基因座的能力。因此，我们有兴趣扩展后验连锁概率（PPL），这是我们在过去十年中一直在开发的一类连锁统计，以明确考虑基因×基因的相互作用。在这份报告中，我们利用了一个新的实施PPL纳入责任类（LC），它提供了一个直接的参数化的基因×基因的相互作用，允许在基因座上进行评估，以依赖于在一个已知的基因座测量的基因型。利用模拟类风湿性关节炎（RA）数据的生成模型的知识，我们选择两个位点进行检查：位点A，其与HLA-DR抗原位点相互作用影响二分RA表型的风险;和位点E，其与DR相互作用影响抗CCP表型的定量水平。这些数据包括两个父母和一个受影响的同胞对（ASP）的核心家庭。我们的研究结果证实了理论工作，即不能利用基因×基因的相互作用，以提高基于受影响的数据结构的二分性状的连锁检测。然而，DR为基础的LC的掺入确实导致明显更高的数量性状PPL。这表明，基因×基因互作可以有效地用于数量性状分析，即使家庭已被确定为相关的二分性状的ASP。
When two genes interact to cause a clinically important phenotype, it would seem reasonable to expect that we could leverage genotypic information at one of the loci in order to improve our ability to detect the other. We were therefore interested in extending the posterior probability of linkage (PPL), a class of linkage statistics we have been developing over the past decade, in order to explicitly allow for gene × gene interaction. In this report we utilize a new implementation of the PPL incorporating liability classes (LCs), which provide a direct parameterization of gene × gene interaction by allowing the penetrances at the locus being evaluated to depend upon measured genotypes at a known locus. With knowledge of the generating model for the simulated rheumatoid arthritis (RA) data, we selected two loci for examination: Locus A, which in interaction with the HLA-DR antigen locus affects risk of the dichotomous RA phenotype; and Locus E, which in interaction with DR affects quantitative levels of the anti-CCP phenotype. The data comprised nuclear families of two parents and an affected sib pair (ASP). Our results confirm theoretical work suggesting that gene × gene interactions CANNOT be leveraged to improve linkage detection for dichotomous traits based on affecteds-only data structures. However, incorporation of DR-based LCs did lead to appreciably higher quantitative trait PPLs. This suggests that gene × gene interactions could be effectively used in quantitative trait analyses even when families have been ascertained as ASPs for a related dichotomous trait.