Two sample Mendelian randomisation (2SMR) is a method to estimate the causal effect of an exposure on an outcome using only summary statistics from genome wide association studies (GWAS). Though conceptually straightforward, there are a number of steps that are required to perform the analysis properly, and they can be cumbersome. The TwoSampleMR package aims to make this easy by combining three important components
The general principles (G. Davey Smith and Ebrahim 2003; George Davey Smith and Hemani 2014), and statistical methods (Pierce and Burgess 2013; Bowden, Davey Smith, and Burgess 2015) can be found elsewhere, here we will just outline how to use the R package.
This package uses the ieugwasr package to connect to the database of thousands of complete GWAS summary data.
To install directly from the GitHub repository do the following:
If you don’t have the
devtools package install it from CRAN using
The workflow for performing MR is as follows:
A diagramatic overview is shown here:
A basic analysis, e.g. the causal effect of body mass index on coronary heart disease, looks like this:
library(TwoSampleMR) # List available GWASs ao <- available_outcomes() # Get instruments exposure_dat <- extract_instruments("ieu-a-2") # Get effects of instruments on outcome outcome_dat <- extract_outcome_data(snps=exposure_dat$SNP, outcomes="ieu-a-7") # Harmonise the exposure and outcome data dat <- harmonise_data(exposure_dat, outcome_dat) # Perform MR res <- mr(dat)
Each step is documented on other pages in the documentation.
The authentication method has changed recently due to the GoogleAuthR method changing. The main differences are that:
mrbase.oauth, rather, there is a directory called
Detailed information is given here: https://github.com/MRCIEU/ieugwasr/blob/master/README.md#authentication