Statistical Identification of Gene-gene Interactions Triggered By Nonlinear Environmental Modulation

Author(s): Xu Liu, Honglang Wang, Yuehua Cui

Journal Name: Current Genomics

Volume 17 , Issue 5 , 2016

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Graphical Abstract:


Complex diseases are often caused by the function of multiple genes, gene-gene (GxG) interactions as well as gene-environment (GxE) interactions. GxG and GE interactions are ubiquitous in nature. Empirical evidences have shown that the effect of GxG interaction on disease risk could be largely modified by environmental changes. Such a GGE triple interaction could be a potential contributing factor to phenotypic plasticity. Although the role of environmental factors moderating genetic influences on disease risk has been broadly recognized, no statistical method has been developed to rigorously assess how environmental changes modify GxG interactions to affect disease risk. To address this issue, we developed a GxGxE triple interaction model in this work. We modeled the environmental modification effect via a varying-coefficient model where the structure of the varying effect is determined by data. Thus the model has the flexibility to assess nonlinear environmental moderation effect on GxG interaction. Simulation and real data analysis were conducted to show the utility of the method. Our approach provides a quantitative framework to assess triple interactions hypothesized in literature.

Keywords: Associate study, Epistasis, Gene-gene-environment triple interaction, Nonlinear interaction, Varying coefficient model.

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Article Details

Year: 2016
Published on: 02 August, 2016
Page: [388 - 395]
Pages: 8
DOI: 10.2174/1389202917666160726150417
Price: $65

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