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MRSamePopTest: introducing a simple falsification test for the two-sample mendelian randomisation ‘same population’ assumption

Published version
Peer-reviewed

Repository DOI


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Authors

Woolf, Benjamin 
Mason, Amy 
Zagkos, Loukas 
Sallis, Hannah 
Munafò, Marcus R 

Abstract

jats:titleAbstract</jats:title>jats:pTwo-sample MR is an increasingly popular method for strengthening causal inference in epidemiological studies. For the effect estimates to be meaningful, variant-exposure and variant-outcome associations must come from comparable populations. A recent systematic review of two-sample MR studies found that, if assessed at all, MR studies evaluated this assumption by checking that the genetic association studies had similar demographics. However, it is unclear if this is sufficient because less easily accessible factors may also be important. Here we propose an easy-to-implement falsification test. Since recent theoretical developments in causal inference suggest that a causal effect estimate can generalise from one study to another if there is exchangeability of effect modifiers, we suggest testing the homogeneity of variant-phenotype associations for a phenotype which has been measured in both genetic association studies as a method of exploring the ‘same-population’ test. This test could be used to facilitate designing MR studies with diverse populations. We developed a simple R package to facilitate the implementation of our proposed test. We hope that this research note will result in increased attention to the same-population assumption, and the development of better sensitivity analyses.</jats:p>

Description

Keywords

Sensitivity analysis, Two-sample Mendelian randomisation, Population homogeneity

Journal Title

BMC Research Notes

Conference Name

Journal ISSN

1756-0500

Volume Title

17

Publisher

Springer Science and Business Media LLC
Sponsorship
Economic and Social Research Council (ES/P000630/1)