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Improving the visualization, interpretation and analysis of two-sample summary data Mendelian randomization via the Radial plot and Radial regression.

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Title: Improving the visualization, interpretation and analysis of two-sample summary data Mendelian randomization via the Radial plot and Radial regression.
Authors: Bowden, J
Spiller, W
Del Greco M, F
Sheehan, N
Thompson, J
Minelli, C
Davey Smith, G
Item Type: Journal Article
Abstract: Background: data furnishing a two-sample Mendelian randomization (MR) 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 MR 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 that is responsible for large differences between IVW and MR-Egger regression estimates. Several additional plots are also proposed for informative data visualization. Conclusions: The Radial plot should be considered in place of the scatter plot for visualizing, analysing and interpreting data from a two-sample summary data MR study. Software is provided to help facilitate its use.
Issue Date: 1-Aug-2018
Date of Acceptance: 14-May-2018
URI: http://hdl.handle.net/10044/1/62766
DOI: https://dx.doi.org/10.1093/ije/dyy101
ISSN: 0300-5771
Publisher: Oxford University Press (OUP)
Start Page: 1264
End Page: 1278
Journal / Book Title: International Journal of Epidemiology
Volume: 47
Issue: 4
Copyright Statement: © 2018 The Author(s). Published by Oxford University Press on behalf of the International Epidemiological Association. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: 0104 Statistics
1117 Public Health And Health Services
Epidemiology
Publication Status: Published
Conference Place: England
Online Publication Date: 2018-06-28
Appears in Collections:Infectious Disease Epidemiology
National Heart and Lung Institute



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