Simultaneously Testing for Marginal Genetic Association and Gene-Environment Interaction
Simultaneously Testing for Marginal Genetic Association and Gene-Environment Interaction
复制标题
DOI：
10.1093/aje/kwr521
复制
发表时间：
2012-07-15
影响因子：
5
通讯作者：
Kooperberg, Charles
中科院分区：
文献类型：
--
作者：
Dai, James Y.;Logsdon, Benjamin A.;Kooperberg, Charles
在这篇文章中，作者建议同时测试边缘遗传关联和基因-环境相互作用，以发现可能参与基因-环境或基因-治疗相互作用的单核苷酸多态性。边际关联估计量和各种交互作用估计量的渐近独立性导致了一种简单而灵活的结合2个检验的方式，允许在估计基因-环境交互作用时利用基因-环境独立性。所提出的检验不同于Kraft等人提出的2-df检验（Kraft赫雷德. 2007;63（2）：111119）。首先，对于遗传关联成分，它测试边缘关联，这通常是推断的主要目标，而不是基因-环境相互作用模型中的主要效应。第二，基因-环境测试组件可以很容易地利用假定的基因-环境独立性，使用仅病例估计或经验贝叶斯估计，这取决于目标是随机试验中的基因-治疗相互作用还是观察性研究中的基因-环境相互作用。通过模拟和妇女健康倡议的遗传研究（1993 - 2005年）说明了拟议的联合测试的使用。
In this article, the authors propose to simultaneously test for marginal genetic association and gene-environment interaction to discover single nucleotide polymorphisms that may be involved in gene-environment or gene-treatment interaction. The asymptotic independence of the marginal association estimator and various interaction estimators leads to a simple and flexible way of combining the 2 tests, allowing for exploitation of gene-environment independence in estimating gene-environment interaction. The proposed test differs from the 2-df test proposed by Kraft et al. (Hum Hered. 2007;63(2):111119) in two respects. First, for the genetic association component, it tests for marginal association, which is often the primary objective in inference, rather than the main effect in a model with gene-environment interaction. Second, the gene-environment testing component can easily exploit putative gene-environment independence using either the case-only estimator or the empirical Bayes estimator, depending on whether the goal is gene-treatment interaction in a randomized trial or gene-environment interaction in an observational study. The use of the proposed joint test is illustrated through simulations and a genetic study (19932005) from the Womens Health Initiative.