Understanding the assumptions underlying Mendelian randomization

Christiaan de Leeuw*, Jeanne Savage, Ioan Gabriel Bucur, Tom Heskes, Danielle Posthuma

*Corresponding author for this work

Research output: Contribution to JournalReview articleAcademicpeer-review

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Abstract

With the rapidly increasing availability of large genetic data sets in recent years, Mendelian Randomization (MR) has quickly gained popularity as a novel secondary analysis method. Leveraging genetic variants as instrumental variables, MR can be used to estimate the causal effects of one phenotype on another even when experimental research is not feasible, and therefore has the potential to be highly informative. It is dependent on strong assumptions however, often producing biased results if these are not met. It is therefore imperative that these assumptions are well-understood by researchers aiming to use MR, in order to evaluate their validity in the context of their analyses and data. The aim of this perspective is therefore to further elucidate these assumptions and the role they play in MR, as well as how different kinds of data can be used to further support them.

Original languageEnglish
Pages (from-to)653-660
Number of pages8
JournalEuropean Journal of Human Genetics
Volume30
Issue number6
Early online date26 Jan 2022
DOIs
Publication statusPublished - Jun 2022

Bibliographical note

Funding Information:
This work was funded by The Netherlands Organization for Scientific Research (NWO VICI 453-14-005 (DP), 645-000-003 (DP), CHiLL 617-001-451 (IGB)) and by F. Hoffman-La Roche AG (CdL).

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to European Society of Human Genetics.

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