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Improving the visualisation, interpretation and analysis of two-sample summary data Mendelian randomization via the radial plot and radial regression

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posted on 2018-06-04, 14:50 authored by Jack Bowden, Wesley Spiller, Fabiola Del Greco, Nuala Sheehan, John Thompson, Cosetta Minelli, George Davey Smith
Background: Summary data furnishing a two-sample Mendelian randomization study are often visualized with the aid of a scatter plot, in which single nucleotide polymorphism (SNP)-outcome associations are plotted against the SNP-exposure associations to provide an immediate picture of the causal effect estimate for each individual variant. It is also convenient to overlay the standard inverse variance weighted (IVW) estimate of causal effect as a fitted slope, to see whether an individual SNP provides evidence that supports, or conflicts with, the overall consensus. Unfortunately, the traditional scatter plot is not the most appropriate means to achieve this aim whenever SNP-outcome associations are estimated with varying degrees of precision and this is reflected in the analysis. Methods: We propose instead to use a small modification of the scatter plot - the Galbraith Radial plot - for the presentation of data and results from an MR study, which enjoys many advantages over the original method. On a practical level it removes the need to recode the genetic data and enables a more straightforward detection of outliers and influential data points. Its use extends beyond the purely aesthetic, however, to suggest a more general modelling framework to operate within when conducting an MR study, including a new form of MR-Egger regression. Results: We illustrate the methods using data from a two-sample Mendelian randomization study to probe the causal effect of systolic blood pressure on coronary heart disease risk, allowing for the possible effects of pleiotropy. The Radial plot is shown to aid the detection of a single outlying variant which is responsible for large differences between IVW and MR-Egger regression estimates. Several additional plots are also proposed for informative data visualisation Conclusion: The Radial plot should be considered in place of the scatter plot for visualising, analysing and interpreting data from a two-sample summary data MR study. Software is provided to help facilitate its use.

History

Citation

International Journal of Epidemiology, 2018, dyy101

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Health Sciences

Version

  • VoR (Version of Record)

Published in

International Journal of Epidemiology

Publisher

Oxford University Press (OUP) for International Epidemiological Association

issn

0300-5771

eissn

1464-3685

Acceptance date

2018-05-01

Copyright date

2018

Available date

2018-09-06

Publisher version

https://academic.oup.com/ije/advance-article/doi/10.1093/ije/dyy101/5046668

Language

en

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