Simulating gene-gene and gene-environment interactions in complex diseases: Gene-Environment iNteraction Simulator 2.

Michele Pinelli,Sergio Cocozza,Gennaro Miele,Giovanni Scala,Roberto Amato

doi:10.1186/1471-2105-13-132

Michele Pinelli, Sergio Cocozza + Show 3 more

Open Access

https://doi.org/10.1186/1471-2105-13-132

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Abstract

BackgroundThe analysis of complex diseases is an important problem in human genetics. Because multifactoriality is expected to play a pivotal role, many studies are currently focused on collecting information on the genetic and environmental factors that potentially influence these diseases. However, there is still a lack of efficient and thoroughly tested statistical models that can be used to identify implicated features and their interactions. Simulations using large biologically realistic data sets with known gene-gene and gene-environment interactions that influence the risk of a complex disease are a convenient and useful way to assess the performance of statistical methods.ResultsThe Gene-Environment iNteraction Simulator 2 (GENS2) simulates interactions among two genetic and one environmental factor and also allows for epistatic interactions. GENS2 is based on data with realistic patterns of linkage disequilibrium, and imposes no limitations either on the number of individuals to be simulated or on number of non-predisposing genetic/environmental factors to be considered. The GENS2 tool 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 Python language 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 from http://sourceforge.net/projects/gensim. The software is released under the GNU General Public License version 3.0.ConclusionsData produced by GENS2 can be used as a benchmark for evaluating statistical tools designed for the identification of gene-gene and gene-environment interactions.

Highlights

The analysis of complex diseases is an important problem in human genetics
Here we describe a method based on the Multi-Logistic Model (MLM) to simulate two genetic and one environmental factors interacting in the determination of a disease risk
To test populations produced by Gene-Environment iNteraction Simulator 2 (GENS2), we performed a set of analyses on some representative populations

Summary

Introduction

Because multifactoriality is expected to play a pivotal role, many studies are currently focused on collecting information on the genetic and environmental factors that potentially influence these diseases. Simulations using large biologically realistic data sets with known gene-gene and gene-environment interactions that influence the risk of a complex disease are a convenient and useful way to assess the performance of statistical methods. Gene-environment interactions (G×E) are expected to influence complex phenotypes, for example, disease risk. The role of G×E is so relevant that it is generally accepted that neglecting them can lead to an underestimation of disease risk, and may explain some of the inconsistencies in replications in different studies [7]. In addition to interactions among genes and environment, interactions among different genetic loci (G×G) can influence disease risk. Epistasis has been identified in human diseases [9,10], and its role in public health has been highlighted [8]

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