Does Accounting for Gene-Environment Interactions Help Uncover Association between Rare Variants and Complex Diseases?
Does Accounting for Gene-Environment Interactions Help Uncover Association between Rare Variants and Complex Diseases?
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DOI：
10.1159/000346825
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发表时间：
2012-01-01
期刊：
影响因子：
1.8
通讯作者：
Witte, John S.
中科院分区：
文献类型：
--
作者：
Kazma, Remi;Cardin, Niall J.;Witte, John S.
目的：为了确定考虑基因-环境（GxE）相互作用是否提高了检测罕见变异与疾病之间关联的能力，我们扩展了三种统计方法，并在各种模拟疾病模型下比较了它们的能力。研究方法：为了测试一组罕见变异与疾病的关联，Min-P使用变异组内的最低p值，CAST（队列等位基因总和测试）使用指示变量来量化变异组内的罕见等位基因，并且SKAT（序列核关联测试）使用基于核机器的逻辑回归。对于每种方法，我们将一个术语的GXE相互作用和测试的关联和相互作用联合。结果如下：当测试疾病与一组罕见变异的关联时，考虑GxE相互作用可以提高特定情况下的功效（纯相互作用或高比例的因果变异与环境相互作用）。然而，这种方法的功效可能会降低，特别是在存在主要遗传或环境影响的情况下。在比较的方法中，优化和加权的SKAT表现最好，无论是测试遗传关联还是与GxE相互作用联合测试。结论：该方法可用于特定情况，但不适用于主要分析。版权所有（C）2013 S. Karger AG，巴塞尔
Objective: To determine whether accounting for gene-environment (GxE) interactions improves the power to detect associations between rare variants and a disease, we have extended three statistical methods and compared their power under various simulated disease models. Methods: To test for association of a group of rare variants with a disease, Min-P uses the lowest p value within the group of variants, CAST (Cohort Allelic Sums Test) uses an indicator variable to quantify the rare alleles within the group of variants, and SKAT (Sequence Kernel Association Test) uses a logistic regression based on kernel machine. For each method, we incorporate a term for the GxE interaction and test for association and interaction jointly. Results: When testing for disease association with a set of rare variants, accounting for GxE interactions can improve power in specific situations (pure interaction or high proportion of causal variants interacting with the environment). However, the power of this approach can decrease, in particular in the presence of main genetic or environmental effects. Among the methods compared, the optimized and weighted SKAT performed best, whether to test for genetic association or to test it jointly with GxE interactions. Conclusion: This approach can be used in specific situations but is not appropriate for a primary analysis. Copyright (C) 2013 S. Karger AG, Basel