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Using the MR-Base platform to investigate risk factors and drug targets for thousands of phenotypes.

ABSTRACT: Mendelian randomization (MR) estimates the causal effect of exposures on outcomes by exploiting genetic variation to address confounding and reverse causation. 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 complementary 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.

SUBMITTER: Walker VM

PROVIDER: S-EPMC6694718 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTwo-sample Mendelian randomization (2SMR) is an increasingly popular epidemiological method that uses genetic variants as instruments for making causal inferences. Clear reporting of methods employed in such studies is important for evaluating their underlying quality. However, the quality of methodological reporting of 2SMR studies is currently unclear. We aimed to assess the reporting quality of studies that used MR-Base, one of the most popular platforms for implementing 2SMR analysis.MethodsWe created a bespoke reporting checklist to evaluate reporting quality of 2SMR studies. We then searched Web of Science Core Collection, PsycInfo, MEDLINE, EMBASE and Google Scholar citations of the MR-Base descriptor paper to identify published MR studies that used MR-Base for any component of the MR analysis. Study screening and data extraction were performed by at least two independent reviewers.ResultsIn the primary analysis, 87 studies were included. Reporting quality was generally poor across studies, with a mean of 53% (SD = 14%) of items reported in each study. Many items required for evaluating the validity of key assumptions made in MR were poorly reported: only 44% of studies provided sufficient details for assessing if the genetic variant associates with the exposure ('relevance' assumption), 31% for assessing if there are any variant-outcome confounders ('independence' assumption), 89% for the assessing if the variant causes the outcome independently of the exposure ('exclusion restriction' assumption) and 32% for assumptions of falsification tests. We did not find evidence of a change in reporting quality over time or a difference in reporting quality between studies that used MR-Base and a random sample of MR studies that did not use this platform.ConclusionsThe quality of reporting of two-sample Mendelian randomization studies in our sample was generally poor. Journals and researchers should consider using the STROBE-MR guidelines to improve reporting quality.

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Using the MR-Base platform to investigate risk factors and drug targets for thousands of phenotypes.

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