Selecting likely causal risk factors from high-throughput experiments using multivariable Mendelian randomization
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Published version
Author(s)
Zuber, Verena
Colijn, Johanna Maria
Klaver, Caroline
Burgess, Stephen
Type
Journal Article
Abstract
Modern high-throughput experiments provide a rich resource to investigate causal determinants of disease risk. Mendelian randomization (MR) is the use of genetic variants as instrumental variables to infer the causal effect of a specific risk factor on an outcome. Multivariable MR is an extension of the standard MR framework to consider multiple potential risk factors in a single model. However, current implementations of multivariable MR use standard linear regression and hence perform poorly with many risk factors. Here, we propose a two-sample multivariable MR approach based on Bayesian model averaging (MR-BMA) that scales to high-throughput experiments. In a realistic simulation study, we show that MR-BMA can detect true causal risk factors even when the candidate risk factors are highly correlated. We illustrate MR-BMA by analysing publicly-available summarized data on metabolites to prioritise likely causal biomarkers for age-related macular degeneration.
Date Issued
2020-01-07
Date Acceptance
2019-11-26
Citation
Nature Communications, 2020, 11 (1)
ISSN
2041-1723
Publisher
Nature Research (part of Springer Nature)
Journal / Book Title
Nature Communications
Volume
11
Issue
1
Copyright Statement
© The Author(s) 2020. This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third partymaterial in this article are included in the article’s Creative Commons license, unlessindicated otherwise in a credit line to the material. If material is not included in thearticle’s Creative Commons license and your intended use is not permitted by statutoryregulation or exceeds the permitted use, you will need to obtain permission directly fromthe copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/31911605
PII: 10.1038/s41467-019-13870-3
Publication Status
Published
Coverage Spatial
England
Article Number
ARTN 29