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Methods Mol Biol. 2018;1793:89-110. doi: 10.1007/978-1-4939-7868-7_7.

Gene-Gene and Gene-Environment Interactions.

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Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.


Identifying gene-gene and gene-environment interactions may help us to better describe the genetic architecture for complex traits. While advances have been made in identifying genetic variants associated with complex traits through more dense panels of genetic variants and larger sample sizes, genome-wide interaction analyses are still limited in power to detect interactions with small effect sizes, rare frequencies, and higher order interactions. This chapter outlines methods for detecting both gene-gene and gene-environment interactions both through explicit tests for interactions (i.e., ones in which the interaction is tested directly) and non-explicit tests (i.e., ones in which an interaction is allowed for in the test, but does not test for the interaction directly) as well as approaches for increasing power by reducing the search space. Issues relating to multiple test correction, replication, and the reporting of interaction results in publications.


Environment; Epistasis; GWAS; Interaction; Power; Replication

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