fastGxE: Powering genome-wide detection of genotype-environment interactions in biobank studies

Overview

fastGxE is a scalable and effective method designed for genome-wide GxE association analysis. fastGxE handles multiple environmental factors and examines one SNP at a time, decomposing the phenotype into SNP main effect, environmental main effects, GxE interaction effects, while controlling for polygenic effects, polygenic interaction effects, and noise heterogeneity (a). fastGxE evaluates various GxE effect size configurations and combines the resulting p-values into a single p-value to test whether the SNP interacts with at least one environmental factor (b). By explicitly modeling polygenic background and heteroscedastic noise, fastGxE generates calibrated p-values for identifying candidate GxE loci (c). Additionally, it utilizes mmSuSiE, an extension of the SuSiE algorithm, to identify the environmental factors driving the detected GxE interactions and employs the stratified Wald test to visualize and support these interactions (d).

Installation

Linux Executable

A statically compiled executable for 64-bit Linux systems is available: fastGxE Linux Executable. This can be used directly on compatible systems.

chmod +x fastgxe
./fastgxe -h

Prerequisites

Ensure the following dependencies are installed on your system:

• C++ Compiler (GCC 9+ or Intel C++ Compiler)
• CMake (Version 3.16 or higher)
• Intel MKL (2024.1)
• GSL (2.7)
• Eigen (3.4.0)
• LBFGSpp
• OpenMP
• CLI
• spdlog

Installation Steps

1. Clone the Repository

git clone https://github.com/chaoning/fastGxE.git
cd fastGxE

2. Set Up Dependencies

Modify CMakeLists.txt to update the paths of external libraries (MKL, GSL, Eigen, LBFGSpp, etc.) according to your system.

3. Build the Project

Run the following commands to compile fastGxE:

mkdir build
cd build
cmake ..
cmake --build .

4. Run fastGxE

After compilation, you can execute FastGxE:

./fastgxe -h

Notes

• If you encounter missing library errors, check that all paths in CMakeLists.txt are correctly configured.
• Use make clean && make to rebuild after modifications.

How to use fastGxE

Check our vignettes.

Citing the work

If you find the fastGxE package or any of the source code in this repository useful for your work, please cite:

Chao Ning and Xiang Zhou (2025). Powering genome-wide detection of genotype-environment interactions in biobank studies.

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