Simulating gene-gene and gene-environment interactions in complex diseases: Gene-Environment iNteraction Simulator 2 (BMC Bioinformatics)

Background: The analysis of complex diseases is an important problem in human genetics. Because multifactoriality isexpected to play a pivotal role, many studies are currently focused on collecting information on the geneticand environmental factors that potentially influence these diseases. However, there is still a lack of efficientand thoroughly tested statistical models that can be used to identify implicated features and theirinteractions. Simulations using large biologically realistic data sets with known gene-gene andgene-environment interactions that influence the risk of a complex disease are a convenient and useful wayto assess the performance of statistical methods. Results: The Gene-Environment iNteraction Simulator 2 (GENS2) simulates interactions among two genetic and oneenvironmental factor and also allows for epistatic interactions. GENS2 is based on data with realisticpatterns of linkage disequilibrium, and imposes no limitations either on the number of individuals to besimulated or on number of non-predisposing genetic/environmental factors to be considered. The GENS2tool is able to simulate gene-environment and gene-gene interactions. To make the Simulator more intuitive,the input parameters are expressed as standard epidemiological quantities. GENS2 is written in Pythonlanguage and takes advantage of operators and modules provided by the simuPOP simulation environment.It can be used through a graphical or a command-line interface and is freely available fromhttp://sourceforge.net/projects/gensim. The software is released under the GNU General Public Licenseversion 3.0. Conclusions: Data produced by GENS2 can be used as a benchmark for evaluating statistical tools designed for theidentification of gene-gene and gene-environment interactions.