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Inferring causal relationships between risk factors and outcomes from GWAS data

Published version
Peer-reviewed

Type

Article

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Authors

Foley, Christopher N 

Abstract

An observational correlation between a suspected risk factor and an outcome does not necessarily imply that interventions on levels of the risk factor will have a causal impact on the outcome ("correlation is not causation"). If genetic variants associated with the risk factor are also associated with the outcome, this increases the plausibility that the risk factor is a causal determinant of the outcome. However, if the genetic variants in the analysis do not have a specific biological link to the risk factor, then causal claims can be spurious. We introduce the Mendelian randomization paradigm for making causal inferences using genetic variants. We consider monogenic analysis, in which genetic variants are taken from a single gene region, and polygenic analysis, which include variants from multiple regions. We focus on answering two questions: when can Mendelian randomization be used to make reliable causal inferences, and when can it make relevant causal inferences.

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Keywords

Journal Title

Annual Review of Genomics and Human Genetics

Conference Name

Journal ISSN

Volume Title

19

Publisher

Annual Reviews, Inc.

Rights

Attribution 4.0 International
Sponsorship
Wellcome Trust (204623/Z/16/Z)
S.B. is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 204623/Z/16/Z).