SlopeHunter: An R package for collider bias correction in conditional GWAS

SlopeHunter is an R package containing tools for correcting for collider bias in conditional Genome-Wide Association Studies (GWAS). For bug reports, feature requests, and questions on technical issues of using the software, please open an Issue.

• Overview
• Documentation
• System Requirements
• Installation Guide
• Illustrative Example
• Citation
• License
• Issues

Overview

Studying genetic associations conditioned on another phenotype, e.g. a study of blood pressure conditional on body mass index, may be influenced by selection bias. An important example - of a growing interest - of these conditional studies is the study of genetic associations with prognosis (e.g. survival, subsequent events). Studies of prognosis, of necessity, can be conducted only in those who have the disease. Selection on disease status can induce associations between causes of incidence with prognosis, potentially leading to selection bias - also termed index event bias or collider bias. The SlopeHunter R package implements the Slope-Hunter method described in Mahmoud et al. 2020 that is developed for correcting collider bias in such conditional Genome-Wide Association Studies.

Documenation

Detailed documentation with usage is at the Slope-Hunter website.

System Requirements

Hardware requirements

The SlopeHunter R package requires only a standard computer for most applications.

Software requirements

The SlopeHunter R package is supported for Windows, Linux and macOS. The package has been tested in R under the following systems:

• Linux: Ubuntu 16.04 (R 4.0.4)
• macOS: Mojave 10.14.6 (R 4.0.4)
• Windows: 10 (R 4.0.4)

R Dependencies

This software requires R (>= 3.5.0). If you do have an older version of R installed on your machine, you may need to install the latest R version from here.

The SlopeHunter R package dependens on the following R packages:

ggplot2 (>= 2.1.0)
mclust
plotly
stats
ieugwasr
data.table (>= 1.14.2)
dplyr
tools

Installation Guide:

To install the package within R, run:

# required only once per machine!
devtools::install_github("Osmahmoud/SlopeHunter")

Illustrative Example

Get started with an example analysis by running the following:

# load the package into your R session
require(SlopeHunter)

# load data of a toy example
data(data_example, package = "SlopeHunter")

# view the first few rows of the data example
head(data_example)

# display description of the data example
help(data_example)

This will show you a detailed description on:

• The instructions on how to run the software.
• The expected outcomes.
• How to explore your outputs.

For more details on usage of the software, run:

help(slopehunter)

Citation

Please do cite both the paper and the software for SlopeHunter as follows:

Mahmoud, O., Dudbridge, F., Davey Smith, G. et al. A robust method for collider bias correction in conditional genome-wide association studies. Nature Communications 13, 619 (2022). (doi: https://doi.org/10.1038/s41467-022-28119-9)

Note: in the citation below, replace the <X.Y.Z> with the version you have used, and the (20XX) with the year in which that version was released.

Mahmoud, O. SlopeHunter: An R package for collider bias correction in conditional GWAS. V<X.Y.Z> (20XX). (doi: https://doi.org/10.5281/zenodo.5617862).

License

This project is covered under the GNU General Public License, version 3.0 (GPL-3.0).