A Unified Model for the Analysis of Gene-Environment Interaction
A Unified Model for the Analysis of Gene-Environment Interaction
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DOI：
10.1093/aje/kwy278
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发表时间：
2019-04-01
影响因子：
5
通讯作者：
Lewinger, Juan Pablo
中科院分区：
文献类型：
--
作者：
Gauderman, W. James;Kim, Andre;Lewinger, Juan Pablo
基因-环境互作对许多复杂性状的形成具有重要意义。在疾病性状的病例对照研究中，逻辑回归是用于将疾病建模为基因（G），环境因素（E），G x E相互作用和调整协变量的标准方法。我们提出了一个替代模型与G的结果，并展示了它如何提供一个统一的框架，从所有常见的G × E测试获得的结果。这些测试包括G x E交互作用的1自由度（df）测试，G和G x E的2-df联合测试，仅限案例和经验贝叶斯测试，以及几个2步测试。在这个统一的模型的背景下，我们提出了一种新的3-DF测试，并证明它提供了强大的电源在广泛的底层G × E相互作用模型。我们使用儿童健康研究（南加州，1993 - 2001）的数据，在全基因组扫描的G x性别相互作用的儿童哮喘中证明了3-DF测试。该扫描发现，在磷酸二酯酶基因4D位点（PDE4D）（一个已知的哮喘相关位点）存在强烈的G x性别相互作用，对男性有强烈影响（每个等位基因比值比= 1.70; P = 3.8 x 10（-8）），对女性几乎没有影响。我们描述了一个软件程序，GxEScan（南加州，洛杉矶，加州大学），它可以用来适应全基因组G × E研究的标准和统一的模型。
Gene-environment (G x E) interaction is important for many complex traits. In a case-control study of a disease trait, logistic regression is the standard approach used to model disease as a function of a gene (G), an environmental factor (E), G x E interaction, and adjustment covariates. We propose an alternative model with G as the outcome and show how it provides a unified framework for obtaining results from all of the common G x E tests. These include the 1-degree-of-freedom (df) test of G x E interaction, the 2-df joint test of G and G x E, the case-only and empirical Bayes tests, and several 2-step tests. In the context of this unified model, we propose a novel 3-df test and demonstrate that it provides robust power across a wide range of underlying G x E interaction models. We demonstrate the 3-df test in a genome-wide scan of G x sex interaction for childhood asthma using data from the Children's Health Study (Southern California, 1993-2001). This scan identified a strong G x sex interaction at the phosphodiesterase gene 4D locus (PDE4D), a known asthma-related locus, with a strong effect in males (per-allele odds ratio = 1.70; P = 3.8 x 10(-8)) and virtually no effect in females. We describe a software program, GxEScan (University of Southern California, Los Angeles, California), which can be used to fit standard and unified models for genome-wide G x E studies.