2020-01-07
Selecting likely causal risk factors from high-throughput experiments using multivariable Mendelian randomization
Publication
Publication
Nature Communications , Volume 11 - Issue 1
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.
| Additional Metadata | |
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| doi.org/10.1038/s41467-019-13870-3, hdl.handle.net/1765/123727 | |
| Nature Communications | |
| Organisation | Department of Epidemiology |
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Zuber, V., Colijn, J., Klaver, C., & Burgess, S. (2020). Selecting likely causal risk factors from high-throughput experiments using multivariable Mendelian randomization. Nature Communications, 11(1). doi:10.1038/s41467-019-13870-3 |
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