This repository contains R code to reproduce Mendelian randomization analyses evaluating the relationship between branch-chain amino acids and blood pressure. The results of these analyses are published as part of:
Murashige et. al. (2022). Extra-cardiac BCAA catabolism lowers blood pressure and protects from heart failure.
The following steps should allow the user to reproduce the BCAA-BP-MR.html
document, which contains additional description of the data sources, methods, and rendered plots/tables/results:
- Clone/download the contents of this repository into a new directory.
- Open
BCAA-BP-MR.qmd
in RStudio and/or render the document using Quarto. This file is a Quarto markdown document, including code and text which when rendered reproduce theBCAA-BP-MR.html
document.
- All required R package dependencies have been captured by the
renv
package (https://rstudio.github.io/renv/index.html), and are stored inrenv.lock
. All required packages will be automatically installed using therenv::restore()
function when the document is rendered. - Summary genetic data used to construct genetic instruments for branch chain amino acids and the corresponding effects on blood pressure traits will be queried from the IEU OpenGWAS Project, or downloaded from the Pan-UK Biobank project into the
Data/
directory. These files are large (~2GB each), and are therefore not included in the repository directly. - The
Data/
directory contains additional information needed to test for enrichment of BCAA-associated genetic variants with genes known to be involved in BCAA metabolism (additional details described inBCAA-BP-MR.qmd
). - Where possible the document reads from cached results located in the
BCAA-BP-MR_cache/
andBCAA-BP-MR_files/
directories to speed up rendering. To render the document entirely from scratch, changecache: true
tocache: false
in the YAML header ofBCAA-BP-MR.qmd
.
- RAM: 32GB (recommended when rendering from scratch, as GWAS summary statistics from Pan-UK Biobank are large; memory requirement should be lower when rendering from cached output or excluding Pan UK Biobank analyses)