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Falsification of the instrumental variable conditions in Mendelian randomization studies in the UK Biobank
Mendelian randomization (MR) is an increasingly popular approach to estimating causal effects. Although the assumptions underlying MR cannot be verified, they imply certain constraints, the instrumental inequalities, which can be used to falsify the MR conditions. However, the instrumental inequalit...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10501946/ https://www.ncbi.nlm.nih.gov/pubmed/37253997 http://dx.doi.org/10.1007/s10654-023-01003-6 |
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author | Guo, Kelly Diemer, Elizabeth W. Labrecque, Jeremy A. Swanson, Sonja A. |
author_facet | Guo, Kelly Diemer, Elizabeth W. Labrecque, Jeremy A. Swanson, Sonja A. |
author_sort | Guo, Kelly |
collection | PubMed |
description | Mendelian randomization (MR) is an increasingly popular approach to estimating causal effects. Although the assumptions underlying MR cannot be verified, they imply certain constraints, the instrumental inequalities, which can be used to falsify the MR conditions. However, the instrumental inequalities are rarely applied in MR. We aimed to explore whether the instrumental inequalities could detect violations of the MR conditions in case studies analyzing the effect of commonly studied exposures on coronary artery disease risk. Using 1077 single nucleotide polymorphisms (SNPs), we applied the instrumental inequalities to MR models for the effects of vitamin D concentration, alcohol consumption, C-reactive protein (CRP), triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol on coronary artery disease in the UK Biobank. For their relevant exposure, we applied the instrumental inequalities to MR models proposing each SNP as an instrument individually, and to MR models proposing unweighted allele scores as an instrument. We did not identify any violations of the MR assumptions when proposing each SNP as an instrument individually. When proposing allele scores as instruments, we detected violations of the MR assumptions for 5 of 6 exposures. Within our setting, this suggests the instrumental inequalities can be useful for identifying violations of the MR conditions when proposing multiple SNPs as instruments, but may be less useful in determining which SNPs are not instruments. This work demonstrates how incorporating the instrumental inequalities into MR analyses can help researchers to identify and mitigate potential bias. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10654-023-01003-6. |
format | Online Article Text |
id | pubmed-10501946 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
spelling | pubmed-105019462023-09-16 Falsification of the instrumental variable conditions in Mendelian randomization studies in the UK Biobank Guo, Kelly Diemer, Elizabeth W. Labrecque, Jeremy A. Swanson, Sonja A. Eur J Epidemiol Methods Mendelian randomization (MR) is an increasingly popular approach to estimating causal effects. Although the assumptions underlying MR cannot be verified, they imply certain constraints, the instrumental inequalities, which can be used to falsify the MR conditions. However, the instrumental inequalities are rarely applied in MR. We aimed to explore whether the instrumental inequalities could detect violations of the MR conditions in case studies analyzing the effect of commonly studied exposures on coronary artery disease risk. Using 1077 single nucleotide polymorphisms (SNPs), we applied the instrumental inequalities to MR models for the effects of vitamin D concentration, alcohol consumption, C-reactive protein (CRP), triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol on coronary artery disease in the UK Biobank. For their relevant exposure, we applied the instrumental inequalities to MR models proposing each SNP as an instrument individually, and to MR models proposing unweighted allele scores as an instrument. We did not identify any violations of the MR assumptions when proposing each SNP as an instrument individually. When proposing allele scores as instruments, we detected violations of the MR assumptions for 5 of 6 exposures. Within our setting, this suggests the instrumental inequalities can be useful for identifying violations of the MR conditions when proposing multiple SNPs as instruments, but may be less useful in determining which SNPs are not instruments. This work demonstrates how incorporating the instrumental inequalities into MR analyses can help researchers to identify and mitigate potential bias. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10654-023-01003-6. Springer Netherlands 2023-05-31 2023 /pmc/articles/PMC10501946/ /pubmed/37253997 http://dx.doi.org/10.1007/s10654-023-01003-6 Text en © The Author(s) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Methods Guo, Kelly Diemer, Elizabeth W. Labrecque, Jeremy A. Swanson, Sonja A. Falsification of the instrumental variable conditions in Mendelian randomization studies in the UK Biobank |
title | Falsification of the instrumental variable conditions in Mendelian randomization studies in the UK Biobank |
title_full | Falsification of the instrumental variable conditions in Mendelian randomization studies in the UK Biobank |
title_fullStr | Falsification of the instrumental variable conditions in Mendelian randomization studies in the UK Biobank |
title_full_unstemmed | Falsification of the instrumental variable conditions in Mendelian randomization studies in the UK Biobank |
title_short | Falsification of the instrumental variable conditions in Mendelian randomization studies in the UK Biobank |
title_sort | falsification of the instrumental variable conditions in mendelian randomization studies in the uk biobank |
topic | Methods |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10501946/ https://www.ncbi.nlm.nih.gov/pubmed/37253997 http://dx.doi.org/10.1007/s10654-023-01003-6 |
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