Mendelian Randomization as an Approach to Assess Causality Using Observational Data

Mendelian randomization refers to an analytic approach to assess the causality of an observed association between a modifiable exposure or risk factor and a clinically relevant outcome. It presents a valuable tool, especially when randomized controlled trials to examine causality are not feasible an...

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Bibliographic Details
Published in:Journal of the American Society of Nephrology Vol. 27; no. 11; p. 3253
Main Authors: Sekula, Peggy, Del Greco M, Fabiola, Pattaro, Cristian, Köttgen, Anna
Format: Journal Article
Language:English
Published: United States 01.11.2016
Subjects:
Cardiovascular Diseases - genetics
Causality
Humans
Mendelian Randomization Analysis
Observational Studies as Topic
Renal Insufficiency, Chronic - genetics
statistical method
mendelian randomization
causality
ISSN:1533-3450, 1533-3450
Online Access:Get more information
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Summary:Mendelian randomization refers to an analytic approach to assess the causality of an observed association between a modifiable exposure or risk factor and a clinically relevant outcome. It presents a valuable tool, especially when randomized controlled trials to examine causality are not feasible and observational studies provide biased associations because of confounding or reverse causality. These issues are addressed by using genetic variants as instrumental variables for the tested exposure: the alleles of this exposure-associated genetic variant are randomly allocated and not subject to reverse causation. This, together with the wide availability of published genetic associations to screen for suitable genetic instrumental variables make Mendelian randomization a time- and cost-efficient approach and contribute to its increasing popularity for assessing and screening for potentially causal associations. An observed association between the genetic instrumental variable and the outcome supports the hypothesis that the exposure in question is causally related to the outcome. This review provides an overview of the Mendelian randomization method, addresses assumptions and implications, and includes illustrative examples. We also discuss special issues in nephrology, such as inverse risk factor associations in advanced disease, and outline opportunities to design Mendelian randomization studies around kidney function and disease.
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ISSN:1533-3450
1533-3450
DOI:10.1681/asn.2016010098