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The Sparse Marginal Epistasis test

The smer package implements a computationally and statistically efficient method for detecting marginal epistasis in genome-wide association studies (GWAS). Find the full package documentation including examples and articles here: Sparse Marginal Epistasis test Documentation.

Key Features

• Hutchinson’s stochastic trace estimator: efficient and scalable computation
• Mailman algorithm: fast vector-by-matrix operation
• Linear mixed model: controls for population structure
• Multimodal Input: incorporates additional data from HDF5 files to improve power in detecting gene-by-gene interactions.
• Optimize for Memory Constraints: Highly configurable block wise processing of the data allows to make the most of available resources. See also How To Optimize the Memory Requirements of SME.
• Parallelization: Utilizes OpenMP for multi-threaded processing.

Installation

You can install the development version of smer from GitHub with:

install.packages("devtools")
devtools::install_github("lcrawlab/sme")

Dependencies

System requirements of the package:

• GNU make
• R (>= 4.4)
• Rhdf5lib (from BioConductor)
• OpenMP (optional)

To install Rhdf5lib, first install the tool BiocManager from CRAN, then install the library using this tool.

if (!require("BiocManager", quietly = TRUE))
    install.packages("BiocManager")
BiocManager::install("Rhdf5lib")

The full list of R dependencies can be found in the DESCRIPTION file.

OpenMP

For OS X and Linux, the OpenMP library can be installed via one of the (shell) commands specified below:

To enable openMP, it may be necessary to configure the compiler flags SHLIB_OPENMP_CXXFLAGS and LDFLAGS in the ~/.R/Makevars file.

Known Issues

Compiling the package requires the compiler to find the libraries for the dependencies. For unix systems, the libraries are typically installed at /usr/local/lib and /usr/local/include. For users using OS X and homebrew, the libraries are typically installed at /opt/homebrew/lib and /opt/homebrew/include.

Non-standard library paths need to be configured. The src/Makevars file configures the compiler flags and considers the LDFLAGS and CPPFLAGS from the ~/.R/Makevars file.

References

• Stamp J, Crawford L (2025). smer: The Sparse Marginal Epistasis Test. R package version 0.0.1, https://lcrawlab.github.io/sme/, https://github.com/lcrawlab/sme.
• Stamp J, Smith Pattillo S, Weinreich D, Crawford L (2025). Sparse modeling of interactions enables fast detection of genome-wide epistasis in biobank-scale studies. biorxiv, https://doi.org/10.1101/2025.01.11.632557
• Stamp J, Crawford L (2024). mvMAPIT: Multivariate Genome Wide Marginal Epistasis Test. R package version 2.0.3, https://lcrawlab.github.io/mvMAPIT/, https://github.com/lcrawlab/mvMAPIT.
• Stamp et al. (2023): Leveraging genetic correlation between traits for epistasis detection in GWAS. G3: Genes, Genomes, Genetics.
• Fu, B., Pazokitoroudi, A., Xue, A., Anand, A., Anand, P., Zaitlen, N., & Sankararaman, S. (2023). A biobank-scale test of marginal epistasis reveals genome-wide signals of polygenic epistasis. bioRxiv.
• Crawford et al. (2017): Detecting epistasis with the marginal epistasis test. PLoS Genetics.
• Devresse et al. (2024): HighFive - Header-only C++ HDF5 interface. https://zenodo.org/records/13120799

These binaries (installable software) and packages are in development.
They may not be fully stable and should be used with caution. We make no claims about them.