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Obesity
Article . 2023 . Peer-reviewed
License: CC BY
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PubMed Central
Article . 2023
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Obesity
Article . 2023
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Challenges in undertaking nonlinear Mendelian randomization

Authors: Kaitlin H. Wade; Fergus W. Hamilton; David Carslake; Naveed Sattar; George Davey Smith; Nicholas J. Timpson;

Challenges in undertaking nonlinear Mendelian randomization

Abstract

AbstractMendelian randomization (MR) is a widely used method that exploits the unique properties of germline genetic variation to strengthen causal inference in relationships between exposures and outcomes. Nonlinear MR allows estimation of the shape of these relationships. In a previous paper, the authors applied linear and nonlinear MR to estimate the effect of BMI on mortality in UK Biobank, providing evidence for a J‐shaped association. However, it is now clear that there are problems with widely used nonlinear MR methods, which draws attention to the likely erroneous nature of the conclusions regarding the shapes of several explored relationships. Here, the authors explore the utility and likely biases of these nonlinear MR methods with the use of a negative control design. Although there remains good evidence for a causal effect of higher BMI increasing the risk of mortality, the pattern of this association across different levels of BMI requires further characterization.

Country
United Kingdom
Keywords

Causality, /dk/atira/pure/core/keywords/population_health_SRI, 330, Perspective, Mendelian Randomization Analysis, name=Bristol Population Health Science Institute, Body Mass Index, Genome-Wide Association Study

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    popularity
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    influence
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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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!
41
Top 10%
Top 10%
Top 1%
Green
hybrid