# Introduction

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

- data management and harmonisation
- the statistical routines to estimate the causal effects
- a large repository of the actual GWAS summary statistics needed to perform the analyses.

The general principles (Davey Smith and Ebrahim 2003; 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.

## Installation

To install directly from the GitHub repository do the following:

If you donâ€™t have the `devtools`

package install it from CRAN using `install.packages("devtools")`

.

## Overview

The workflow for performing MR is as follows:

- Select instruments for the exposure (perform LD clumping if necessary)
- Extract the instruments from the MR Base GWAS database for the outcomes of interest
- Harmonise the effect sizes for the instruments on the exposures and the outcomes to be each for the same reference allele
- Perform MR analysis, sensitivity analyses, create plots, compile reports

A diagramatic overview is shown here: