Tests for Gene-Environment Interaction From Case-Control Data: A Novel Study of Type I Error, Power and Designs
Tests for Gene-Environment Interaction From Case-Control Data: A Novel Study of Type I Error, Power and Designs
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DOI：
10.1002/gepi.20337
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发表时间：
2008-11-01
影响因子：
2.1
通讯作者：
Chatterjee, Nilanjan
中科院分区：
文献类型：
--
作者：
Mukherjee, Bhramar;Ahn, Jaeil;Chatterjee, Nilanjan
为了评估与遗传易感性和环境暴露的联合效应相关的疾病风险，流行病学研究人员经常从病例对照研究中测试非倍增的基因-环境效应。在这篇文章中，我们提出了一个比较研究的四个替代测试的相互作用：（i）标准的病例对照方法，（ii）仅病例的方法，这需要一个假设的基因环境独立的基础人口，（iii）两步法，根据基因-环境独立性假设的统计检验，在仅病例和病例对照估计量之间做出决定;以及（iv）一种新的统计贝叶斯（EB）方法，结合病例对照和病例只有估计取决于样本量和强度的基因环境关联的数据。我们评估的方法，综合I型错误和权力，平均相对于不同的情况下，可能会出现在实践中的基因-环境关联。这些独特的研究表明，新的EB程序总体上是一个有前途的方法，从病例对照研究中检测基因-环境相互作用。特别是，EB程序，不像的情况下，只有或两个步骤的方法，可以密切保持理想的I型错误的基因环境依赖的现实情况下，但可以大大更强大的比传统的病例对照分析时，基因环境的独立性假设得到满足，准确或近似。我们的研究还揭示了一些非传统的病例对照设计的潜在效用，这些设计的样本对照率低于病例。除了模拟研究，我们还说明了不同的方法，通过分析相互作用的两个常用的研究基因，N-乙酰转移酶2型和谷胱甘肽S-转移酶M1，吸烟和饮食暴露，在一个大型的病例对照研究结直肠癌。Genet.流行病学32：615-626，2008. 2008年发布Wiley-Liss，Inc.（匕首）
To evaluate the risk of a disease associated with the joint effects of genetic susceptibility and environmental exposures, epidemiologic researchers often test for non-multiplicative gene-environment effects from case-control studies. In this article, we present a comparative study of four alternative tests for interactions: (i) the standard case-control method; (ii) the case-only method, which requires an assumption of gene-environment independence for the underlying population; (iii) a two-step method that decides between the case-only and case-control estimators depending on a statistical test for the gene-environment independence assumption and (iv) a novel empirical-Bayes (EB) method that combines the case-control and case-only estimators depending on the sample size and strength of the gene-environment association in the data. We evaluate the methods in terms of integrated Type I error and power, averaged with respect to varying scenarios for gene-environment association that are likely to appear in practice. These unique studies suggest that the novel EB procedure overall is a promising approach for detection of gene-environment interactions from case-control studies. In particular, the EB procedure, unlike the case-only or two-step methods, can closely maintain a desired Type I error under realistic scenarios of gene-environment dependence and yet can be substantially more powerful than the traditional case-control analysis when the gene-environment independence assumption is satisfied, exactly or approximately. Our studies also reveal potential utility of some non-traditional case-control designs that samples controls at a smaller rate than the cases. Apart from the simulation studies, we also illustrate the different methods by analyzing interactions of two commonly studied genes, N-acetyl transferase type 2 and glutathione s-transferase M1, with smoking and dietary exposures, in a large case-control study of colorectal cancer. Genet. Epidemiol. 32:615-626, 2008. Published 2008 Wiley-Liss, Inc.(dagger)