학술논문

MRSamePopTest: introducing a simple falsification test for the two-sample mendelian randomisation ‘same population’ assumption
Document Type
article
Source
BMC Research Notes, Vol 17, Iss 1, Pp 1-6 (2024)
Subject
Sensitivity analysis
Two-sample Mendelian randomisation
Population homogeneity
Medicine
Biology (General)
QH301-705.5
Science (General)
Q1-390
Language
English
ISSN
1756-0500
Abstract
Abstract Two-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.