基因-环境相互作用：变量选择的观点
Gene-Environment Interaction: A Variable Selection Perspective
摘要：
基因-环境相互作用对阐明复杂疾病的遗传基础具有重要意义，而不仅仅是多个遗传因素及其相互作用（或上位性）的联合作用。过去，G $\times$ E相互作用主要在遗传关联研究的框架内进行。由于环境影响的复杂形式和包括基因表达和SNP在内的大量遗传因素的存在，G $\times$ E相互作用的高维性促使了最近开发用于剖析G $\times$ E相互作用的惩罚变量选择方法，这在大多数已发表的遗传相互作用研究综述中被忽视。在这篇文章中，我们首先调查现有的基因-环境和基因-基因相互作用的概述。然后，在简要介绍变量选择方法之后，我们分别回顾了各种概念模型下的边际范式和联合范式中的惩罚和相关变量选择方法。讨论的优势和局限性，以及为G $\times$ E研究量身定制的变量选择方法的计算方面也已提供。
英文摘要：
Gene-environment interactions have important implications to elucidate the genetic basis of complex diseases beyond the joint function of multiple genetic factors and their interactions (or epistasis). In the past, G$\times$E interactions have been mainly conducted within the framework of genetic association studies. The high dimensionality of G$\times$E interactions, due to the complicated form of environmental effects and presence of a large number of genetic factors including gene expressions and SNPs, has motivated the recent development of penalized variable selection methods for dissecting G$\times$E interactions, which has been ignored in majority of published reviews on genetic interaction studies. In this article, we first survey existing overviews on both gene-environment and gene-gene interactions. Then, after a brief introduction on the variable selection methods, we review penalization and relevant variable selection methods in marginal and joint paradigms respectively under a variety of conceptual models. Discussions on strengths and limitations, as well as computational aspects of the variable selection methods tailored for G$\times$E studies have also been provided.
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