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Contents

  • Overview
  • System Requirements
  • Installation Guide
  • Demo
  • URLs and References

Overview

Studying genotype-by-environment interaction (GEI) is fundamental in understanding complex trait variations. Identifying genetic variants with GEI effects is challenging because the GEI analysis generally has low power. MTAGEI (Multi-Trait Analysis of Gene-Environment Interactions) is a powerful, robust, and computationally efficient method to test the interaction between a gene and environmental groups on multiple traits in large-scale datasets, such as the UK Biobank. More details about MTAGEI can be found in Luo et al (2023).

Specifically, MTAGEI package has functions to

  • compute the summary statistics with different types of data input adjusting for the potential overlapping samples under different assumption of genetic marginal effects; and
  • perform summary-statistics-based multi-trait analysis of gene-environment interaction (GEI) tests or genetic main effect and GEI joint effect for both common and rare variants.

Fig 1

System Requirements

The package development version is tested on the following systems:

Mac OSX: Mojave version 10.14.6 (R version 3.6.0)

Windows 10 (R version 3.6.1)

The CRAN package should be compatible with Windows and Mac operating systems.

Installing Guide

MTAGEI package requires R with version 3.6.1 or higher, which can be downloaded and installed from Github.

install.packages("MTAGEI.tar.gz", repos = NULL, type = "source")

Package dependencies

MTAGEI package depends on several R packages, which will be downloaded before installing MTAGEI. MTAGEI also uses non-exported R code from R packages ACAT and SKAT. The MTAGEI package functions with all packages in their versions as they appear on CRAN or github on January 23, 2020 and October 28, 2021, respectively. The versions of software are, specifically:

MASS (>= 7.3-51.4),
Matrix (>= 1.2-17),
caret (>= 6.0-84),
stats,
utils,
gtools (>= 3.8.1),
SPAtest (>= 3.0.0),
survival (>= 3.2-3),
SimCorMultRes (>= 1.7.0),
SKAT (>= 1.3.2.1),
expm (>= 0.999-4),
CompQuadForm (>= 1.4.3),
caret (>=6.0-84)

Demo

Detailed instructions can be found in Vignetts/MTAGEI.html file. Preview

URLs

ldsc website: https://github.com/bulik/ldsc/wiki/Heritability-and-Genetic-Correlation

Genetic correlation: https://media.nature.com/original/nature-assets/ng/journal/v47/n11/extref/ng.3406-S2.csv

References

Bulik-Sullivan, Brendan, Hilary K Finucane, Verneri Anttila, Alexander Gusev, Felix R Day, John RB Perry, Nick Patterson, et al. 2015. “An Atlas of Genetic Correlations Across Human Diseases and Traits.” Nat. Genet. 47 (11): 1236–41.

Bulik-Sullivan, Brendan K, Po-Ru Loh, Hilary K Finucane, Stephan Ripke, Jian Yang, Nick Patterson, Mark J Daly, et al. 2015. “LD Score Regression Distinguishes Confounding from Polygenicity in Genome-Wide Association Studies.” Nature Genetics 47 (3): 291.

Luo, Lan, Devan V Mehrotra, Judong Shen, and Zheng-Zheng Tang. 2023. “Multi-Trait Analysis of Gene-by-Environment Interactions in Large-scale Genetic Studies.” Submitted to Biostatistics.

Luo, Lan, Judong Shen, Hong Zhang, Aparna Chhibber, Devan V Mehrotra, and Zheng-Zheng Tang. 2020. “Multi-Trait Analysis of Rare-Variant Association Summary Statistics Using MTAR.” Nat. Commun. 11 (1): 1–11.

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