mrrobust: Stata package for two-sample Mendelian randomization analyses using summary data

Short video introduction

Click here for a short video demonstrating the use of the package.

Overview

The mrrobust package is a collection of commands for performing two-sample Mendelian randomization analyses using summary data of genotype-phenotype and genotype-outcome associations.

Such data can be obtained from repositories such as MR-Base http://www.mrbase.org (Hemani et al. 2016).

The package contains the following commands:

• mrratio implements the standard instrumental variable ratio (Wald) estimate with a choice of standard errors/confidence intervals.
• mrivests automates calling mrratio on all the selected genotypes in your dataset.
• mregger implements the IVW and MR-Egger regression approaches introduced in Bowden et al. 2015.
• mreggersimex implements the simulation extrapolation algorithm for the MR-Egger model.
• mreggerplot implements a scatter plot with fitted line (either from IVW, MR-Egger, or weighted median estimators) and confidence interval.
• mrmedian and mrmedianobs implement the unweighted, weighted, and penalized weighted median IV estimators robust to 50% invalid instruments in Bowden et al. 2016.
• mrmodal implements the zero modal estimator of Hartwig et al. 2017.
• mrmodalplot plot of density used in modal estimator.
• mrforest implements a forest plot of genotype specific IV estimates and estimates from models (e.g. IVW and MR-Egger).
• mrfunnel funnel plot of genotype specific IV estimates.

Installation

Stata version 13 and later

First install the dependencies. The package uses Ben Jann's addplot, kdens, and moremata packages, the heterogi command (Orsini et al.), the metan command (Harris et al.), and the grc1leg command (Wiggins). Install those using the following commands:

. ssc install addplot
. ssc install kdens
. ssc install moremata
. ssc install heterogi
. ssc install metan
. net install grc1leg, from(http://www.stata.com/users/vwiggins)

To install mrrobust issue in Stata (in versions 13 and above):

. net install mrrobust, from(https://raw.github.com/remlapmot/mrrobust/master/) replace

If you have previously installed the package and the net install command above fails with an error message that there are two copies of the package installed simply run adoupdate. Also run adoupdate to check for updates. To update the package if you know an update is available run:

. adoupdate mrrobust, update

There is a summary helpfile:

. help mrrobust

The helpfile for each command has an example near the end:

. help mrratio
. help mrivests
. help mregger
. help mreggersimex
. help mreggerplot
. help mrmedian
. help mrmedianobs
. help mrmodal
. help mrmodalplot
. help mrforest
. help mrfunnel

To uninstall the package, issue in Stata:

. ado uninstall mrrobust

If this fails with an error mentioning multiple citations/instances of the package being installed simply issue adoupdate mrrobust which will leave you with just one instance of the package (which can then be uninstalled).

Stata version 12 and earlier

The net install syntax for installing mrrobust above does not work under Stata version 12 (and earlier versions) because this webpage has an address starting with https rather than http. However, the installation commands for the other dependencies should work.

To download mrrobust manually click the green "Clone or download" button above and then download as a zip archive. Then extract the zip archive on your computer. Then move the extracted files to your adopath.

If you need to install the other commands manually:

• The moremata package is available as a zip file here http://fmwww.bc.edu/repec/bocode/m/moremata.zip.
• The addplot package is available here http://fmwww.bc.edu/repec/bocode/a/addplot.zip.
• The heterogi command is available here https://ideas.repec.org/c/boc/bocode/s449201.html.
• The kdens package is available here http://fmwww.bc.edu/repec/bocode/k/kdens.zip.
• The metan command is available here https://ideas.repec.org/c/boc/bocode/s456798.html.
• The grc1leg ado-file is here http://www.stata.com/users/vwiggins/grc1leg/grc1leg.ado and the helpfile is here http://www.stata.com/users/vwiggins/grc1leg/grc1leg.hlp

Extract the zip archives and save all files on your adopath.

To uninstall a manual installation simply delete the files you placed on your adopath.

Authors

Tom Palmer, Wesley Spiller, Neil Davies

Citation

Spiller W, Davies NM, Palmer TM. Software Application Profile: mrrobust - A tool for performing two-sample summary Mendelian randomization analyses. bioRxiv, published online 25th May 2017. https://doi.org/10.1101/142125

References

• Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. International Journal of Epidemiology, 2015, 44, 2, 512-525. http://dx.doi.org/10.1093/ije/dyv080
• Bowden J, Davey Smith G, Haycock PC, Burgess S. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genetic Epidemiology, published online 7 April 2016. http://dx.doi.org/10.1002/gepi.21965
• Hartwig FP, Davey Smith G, Bowden J. Robust inference in two-sample Mendelian randomisation via the zero modal pleiotropy assumption. bioRxiv. http://dx.doi.org/10.1101/126102
• Hemani G et al. MR-Base: a platform for systematic causal inference across the phenome using billions of genetic associations. bioRxiv, 2016. https://doi.org/10.1101/078972

Acknowledgements

Thanks to Michael Holmes, Caroline Dale, Amy Taylor, Rebecca Richmond, Judith Brand, Yanchun Bao, Kawthar Al-Dabhani, Michalis Katsoulis, and Ghazaleh Fatemifar for helpful feedback and suggestions.