Bayesian mixture modeling of gene-environment and gene-gene interactions.

Bayesian mixture modeling of gene-environment and gene-gene interactions.
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DOI:
10.1002/gepi.20429
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发表时间:
2010-01
影响因子:
2.1
通讯作者:
Hung, Rayjean J.
Hung, Rayjean J.
中科院分区:
医学4区
文献类型:
--
作者:
Wakefield, Jon;De Vocht, Frank;Hung, Rayjean J.

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随着快速和相对便宜的基因分型技术的出现,当基因和环境因素的数量可能很大时,现在有机会尝试识别基因-环境和基因-基因相互作用。不幸的是,参数空间的维数导致可能被研究的可能相互作用的数量的计算爆炸。包含所有交互作用和主效应的完整模型可能不稳定,因为大量估计参数会产生较宽的置信区间。我们描述了一个分层的混合模型,允许所有的相互作用进行调查,同时,但假设的影响来自一个混合物之前的两个组件,一个反映了小的零效应和第二流行病学上的显着影响。来自前者的影响被有效地设置为零,因此增加了用于检测真实的信号的功率。先前的框架非常灵活,可以将实质性信息纳入分析。我们首先使用模拟来说明这些方法,然后使用中欧和东欧肺癌病例对照研究的数据。
With the advent of rapid and relatively cheap genotyping technologies there is now the opportunity to attempt to identify gene-environment and gene-gene interactions when the number of genes and environmental factors is potentially large. Unfortunately the dimensionality of the parameter space leads to a computational explosion in the number of possible interactions that may be investigated. The full model that includes all interactions and main effects can be unstable, with wide confidence intervals arising from the large number of estimated parameters. We describe a hierarchical mixture model that allows all interactions to be investigated simultaneously, but assumes the effects come from a mixture prior with two components, one that reflects small null effects and the second for epidemiologically significant effects. Effects from the former are effectively set to zero, hence increasing the power for the detection of real signals. The prior framework is very flexible, which allows substantive information to be incorporated into the analysis. We illustrate the methods first using simulation, and then on data from a case-control study of lung cancer in Central and Eastern Europe.
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