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Mendelian Randomization: A Review of Methods for the Prevention, Assessment, and Discussion of Pleiotropy in Studies Using the Fat Mass and Obesity-Associated Gene as an Instrument for Adiposity

Pleiotropy assessment is critical for the validity of Mendelian randomization (MR) analyses, and its management remains a challenging task for researchers. This review examines how the authors of MR studies address bias due to pleiotropy in practice. We reviewed Pubmed, Medline, Embase and Web of Sc...

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Autores principales: Mbutiwi, Fiston Ikwa Ndol, Dessy, Tatiana, Sylvestre, Marie-Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855149/
https://www.ncbi.nlm.nih.gov/pubmed/35186031
http://dx.doi.org/10.3389/fgene.2022.803238
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author Mbutiwi, Fiston Ikwa Ndol
Dessy, Tatiana
Sylvestre, Marie-Pierre
author_facet Mbutiwi, Fiston Ikwa Ndol
Dessy, Tatiana
Sylvestre, Marie-Pierre
author_sort Mbutiwi, Fiston Ikwa Ndol
collection PubMed
description Pleiotropy assessment is critical for the validity of Mendelian randomization (MR) analyses, and its management remains a challenging task for researchers. This review examines how the authors of MR studies address bias due to pleiotropy in practice. We reviewed Pubmed, Medline, Embase and Web of Science for MR studies published before 21 May 2020 that used at least one single-nucleotide polymorphism (SNP) in the fat mass and obesity-associated (FTO) gene as instrumental variable (IV) for body mass index, irrespective of the outcome. We reviewed: 1) the approaches used to prevent pleiotropy, 2) the methods cited to detect or control the independence or the exclusion restriction assumption highlighting whether pleiotropy assessment was explicitly stated to justify the use of these methods, and 3) the discussion of findings related to pleiotropy. We included 128 studies, of which thirty-three reported one approach to prevent pleiotropy, such as the use of multiple (independent) SNPs combined in a genetic risk score as IVs. One hundred and twenty studies cited at least one method to detect or account for pleiotropy, including robust and other IV estimation methods (n = 70), methods for detection of heterogeneity between estimated causal effects across IVs (n = 72), methods to detect or account associations between IV and outcome outside thought the exposure (n = 85), and other methods (n = 5). Twenty-one studies suspected IV invalidity, of which 16 explicitly referred to pleiotropy, and six incriminating FTO SNPs. Most reviewed MR studies have cited methods to prevent or to detect or control bias due to pleiotropy. These methods are heterogeneous, their triangulation should increase the reliability of causal inference.
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spelling pubmed-88551492022-02-19 Mendelian Randomization: A Review of Methods for the Prevention, Assessment, and Discussion of Pleiotropy in Studies Using the Fat Mass and Obesity-Associated Gene as an Instrument for Adiposity Mbutiwi, Fiston Ikwa Ndol Dessy, Tatiana Sylvestre, Marie-Pierre Front Genet Genetics Pleiotropy assessment is critical for the validity of Mendelian randomization (MR) analyses, and its management remains a challenging task for researchers. This review examines how the authors of MR studies address bias due to pleiotropy in practice. We reviewed Pubmed, Medline, Embase and Web of Science for MR studies published before 21 May 2020 that used at least one single-nucleotide polymorphism (SNP) in the fat mass and obesity-associated (FTO) gene as instrumental variable (IV) for body mass index, irrespective of the outcome. We reviewed: 1) the approaches used to prevent pleiotropy, 2) the methods cited to detect or control the independence or the exclusion restriction assumption highlighting whether pleiotropy assessment was explicitly stated to justify the use of these methods, and 3) the discussion of findings related to pleiotropy. We included 128 studies, of which thirty-three reported one approach to prevent pleiotropy, such as the use of multiple (independent) SNPs combined in a genetic risk score as IVs. One hundred and twenty studies cited at least one method to detect or account for pleiotropy, including robust and other IV estimation methods (n = 70), methods for detection of heterogeneity between estimated causal effects across IVs (n = 72), methods to detect or account associations between IV and outcome outside thought the exposure (n = 85), and other methods (n = 5). Twenty-one studies suspected IV invalidity, of which 16 explicitly referred to pleiotropy, and six incriminating FTO SNPs. Most reviewed MR studies have cited methods to prevent or to detect or control bias due to pleiotropy. These methods are heterogeneous, their triangulation should increase the reliability of causal inference. Frontiers Media S.A. 2022-02-04 /pmc/articles/PMC8855149/ /pubmed/35186031 http://dx.doi.org/10.3389/fgene.2022.803238 Text en Copyright © 2022 Mbutiwi, Dessy and Sylvestre. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Mbutiwi, Fiston Ikwa Ndol
Dessy, Tatiana
Sylvestre, Marie-Pierre
Mendelian Randomization: A Review of Methods for the Prevention, Assessment, and Discussion of Pleiotropy in Studies Using the Fat Mass and Obesity-Associated Gene as an Instrument for Adiposity
title Mendelian Randomization: A Review of Methods for the Prevention, Assessment, and Discussion of Pleiotropy in Studies Using the Fat Mass and Obesity-Associated Gene as an Instrument for Adiposity
title_full Mendelian Randomization: A Review of Methods for the Prevention, Assessment, and Discussion of Pleiotropy in Studies Using the Fat Mass and Obesity-Associated Gene as an Instrument for Adiposity
title_fullStr Mendelian Randomization: A Review of Methods for the Prevention, Assessment, and Discussion of Pleiotropy in Studies Using the Fat Mass and Obesity-Associated Gene as an Instrument for Adiposity
title_full_unstemmed Mendelian Randomization: A Review of Methods for the Prevention, Assessment, and Discussion of Pleiotropy in Studies Using the Fat Mass and Obesity-Associated Gene as an Instrument for Adiposity
title_short Mendelian Randomization: A Review of Methods for the Prevention, Assessment, and Discussion of Pleiotropy in Studies Using the Fat Mass and Obesity-Associated Gene as an Instrument for Adiposity
title_sort mendelian randomization: a review of methods for the prevention, assessment, and discussion of pleiotropy in studies using the fat mass and obesity-associated gene as an instrument for adiposity
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855149/
https://www.ncbi.nlm.nih.gov/pubmed/35186031
http://dx.doi.org/10.3389/fgene.2022.803238
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