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Outlier Detection in Mendelian Randomization

Authors: Maximilian M. Mandl; Anne‐Laure Boulesteix; Stephen Burgess; Verena Zuber;

Outlier Detection in Mendelian Randomization

Abstract

ABSTRACT Mendelian randomization (MR) uses genetic variants as instrumental variables to infer causal effects of exposures on an outcome. One key assumption of MR is that the genetic variants used as instrumental variables are independent of the outcome conditional on the risk factor and unobserved confounders. Violations of this assumption, that is, the effect of the instrumental variables on the outcome through a path other than the risk factor included in the model (which can be caused by pleiotropy), are common phenomena in human genetics. Genetic variants, which deviate from this assumption, appear as outliers to the MR model fit and can be detected by the general heterogeneity statistics proposed in the literature, which are known to suffer from overdispersion, that is, too many genetic variants are declared as false outliers. We propose a method that corrects for overdispersion of the heterogeneity statistics in uni‐ and multivariable MR analysis by making use of the estimated inflation factor to correctly remove outlying instruments and therefore account for pleiotropic effects. Our method is applicable to summary‐level data.

Keywords

FOS: Computer and information sciences, instrumental variables, Models, Statistical, Genetic Variation, Genetic Pleiotropy, outlier detection, Mendelian Randomization Analysis, Causality, Methodology (stat.ME), Risk Factors, pleiotropy, Mendelian randomization, invalid instruments, Humans, Computer Simulation, Statistics - Methodology, Research Article

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
1
Average
Average
Average
Green
hybrid