Gene-environment interactions in genome-wide association studies: current approaches and new directions.
Gene-environment interactions in genome-wide association studies: current approaches and new directions.
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DOI：
10.1111/jcpp.12114
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Biernacka JM
中科院分区：
文献类型：
--
作者：
Winham SJ;Biernacka JM
长期以来，复杂的精神病特征被认为是遗传和环境因素相结合的结果，基因-环境相互作用被认为在行为表型和精神疾病的易感性和进展中起着至关重要的作用。研究假设的基因-环境相互作用的候选基因研究现在在人类遗传学研究中相当普遍，并且随着向全基因组关联研究的转变，全基因组基因-环境相互作用研究开始出现。我们总结了基因-环境相互作用背后的基本思想，并概述了全基因组分析背景下可能的研究设计和传统分析方法。然后，我们讨论了新的方法，超越了传统的策略，分析环境因素和每个多态性之间的相互作用。两步过滤方法，减少了相互作用的多态性测试的数量，可以大大增加全基因组基因环境研究的力量。新的分析方法，包括数据挖掘方法，基因水平和路径水平的分析，也有能力提高我们对复杂的遗传和环境因素如何相互作用影响心理和精神特征的理解。然而，这些方法在行为和心理健康研究中还没有得到太多的利用。虽然研究基因-环境相互作用的方法是可用的，有必要进一步发展和扩展这些方法，以确定基因-环境相互作用的背景下，全基因组关联研究。这些新的方法需要应用于心理学和精神病学的研究。
Complex psychiatric traits have long been thought to be the result of a combination of genetic and environmental factors, and gene-environment interactions are thought to play a crucial role in behavioral phenotypes and the susceptibility and progression of psychiatric disorders. Candidate gene studies to investigate hypothesized gene-environment interactions are now fairly common in human genetic research, and with the shift towards genome-wide association studies, genome-wide gene-environment interaction studies are beginning to emerge. We summarize the basic ideas behind gene-environment interaction, and provide an overview of possible study designs and traditional analysis methods in the context of genome-wide analysis. We then discuss novel approaches beyond the traditional strategy of analyzing the interaction between the environmental factor and each polymorphism individually. Two-step filtering approaches that reduce the number of polymorphisms tested for interactions can substantially increase the power of genome-wide gene-environment studies. New analytical methods including data-mining approaches, and gene-level and pathway-level analyses, also have the capacity to improve our understanding of how complex genetic and environmental factors interact to influence psychological and psychiatric traits. Such methods, however, have not yet been utilized much in behavioral and mental health research. Although methods to investigate gene-environment interactions are available, there is a need for further development and extension of these methods to identify gene-environment interactions in the context of genome-wide association studies. These novel approaches need to be applied in studies of psychology and psychiatry.
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