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Gene--environment-wide association studies: emerging approaches Thomas DNat Rev Genet 2010[Apr]; 11 (4): 259-72Despite the yield of recent genome-wide association (GWA) studies, the identified variants explain only a small proportion of the heritability of most complex diseases. This unexplained heritability could be partly due to gene--environment (GxE) interactions or more complex pathways involving multiple genes and exposures. This Review provides a tutorial on the available epidemiological designs and statistical analysis approaches for studying specific GxE interactions and choosing the most appropriate methods. I discuss the approaches that are being developed for studying entire pathways and available techniques for mining interactions in GWA data. I also explore methods for marrying hypothesis-driven pathway-based approaches with 'agnostic' GWA studies.|*Environment[MESH]|Data Mining[MESH]|Epigenesis, Genetic[MESH]|Genetic Predisposition to Disease[MESH]|Genome-Wide Association Study/*methods/statistics & numerical data/trends[MESH]|Humans[MESH]|Models, Genetic[MESH]|Risk Factors[MESH] |
