Abstract
Mendelian randomization (MR) uses genetic information to strengthen causal inference concerning the effect of exposures on outcomes. This method has a broad range of applications, including investigating risk factors and appraising potential targets for intervention. MR-Base has become established as a freely accessible, online platform, which combines a database of complete genome-wide association study results with an interface for performing Mendelian randomization and sensitivity analyses. This allows the user to explore millions of potentially causal associations. MR-Base is available as a web application or as an R package. The technical aspects of the tool have previously been documented in the literature. The present article is complimentary to this as it focuses on the applied aspects. Specifically, we describe how MR-Base can be used in several ways, including to perform novel causal analyses, replicate results and enable transparency, amongst others. We also present three use cases, which demonstrate important applications of Mendelian randomization and highlight the benefits of using MR-Base for these types of analyses.
Highlights
Mendelian randomization (MR) is a method for strengthening the causal inference concerning the effects of risk factors and exposures on outcome traits using genetic variation[1]
Two-sample Mendelian randomization is an extension of this method that allows the use of summary statistics from genomewide association studies (GWASs) in place of individual-level genetic data
MR-Base[2] combines a database of summary statistics on traits and health outcomes from over 20,000 GWASs, with an interface for performing two-sample Mendelian randomization to simplify the implementation of this method
Summary
Mendelian randomization (MR) is a method for strengthening the causal inference concerning the effects of risk factors and exposures on outcome traits using genetic variation[1]. Two-sample Mendelian randomization is an extension of this method that allows the use of summary statistics from genomewide association studies (GWASs) in place of individual-level genetic data. MR-Base[2] combines a database of summary statistics on traits and health outcomes from over 20,000 GWASs, with an interface for performing two-sample Mendelian randomization to simplify the implementation of this method. As of February 2019, the repository was populated by curated and harmonized datasets corresponding to over 250 billion single nucleotide polymorphisms (SNP)-trait associations[3]. It is available via a web interface or through the package ‘TwoSampleMR’ for R. Useful links, including these, can be found in Box 2
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