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Investigating the association of atopic dermatitis with ischemic stroke and coronary heart disease: A mendelian randomization study
Background: Atopic dermatitis (AD) is the most common chronic skin inflammatory disease. Prior observational studies have reported inconsistent results on the association of AD with ischemic stroke and coronary heart disease. In this study, we applied two-sample Mendelian randomization (MR) to evalu...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468876/ https://www.ncbi.nlm.nih.gov/pubmed/36110212 http://dx.doi.org/10.3389/fgene.2022.956850 |
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author | Huang, Jian Gui, Ying Wu, Jing Xie, Yubo |
author_facet | Huang, Jian Gui, Ying Wu, Jing Xie, Yubo |
author_sort | Huang, Jian |
collection | PubMed |
description | Background: Atopic dermatitis (AD) is the most common chronic skin inflammatory disease. Prior observational studies have reported inconsistent results on the association of AD with ischemic stroke and coronary heart disease. In this study, we applied two-sample Mendelian randomization (MR) to evaluate the causal effect of AD on ischemic stroke and coronary heart disease. Methods: Twelve single-nucleotide polymorphisms robustly associated with AD (p < 5 × 10(–8)) were obtained from a genome-wide association study that included 10,788 cases and 30,047 controls by the EArly Genetics and Life course Epidemiology (EAGLE) Consortium (excluding the 23andMe study). The corresponding data for ischemic stroke (34,217 cases and 406,111 controls), large artery stroke (4,373 cases and 406,111 controls), cardioembolic stroke (7,193 cases and 406,111 controls), small vessel stroke (5,386 cases and 192,662 controls), coronary heart disease (122,733 cases and 424,528 controls), and myocardial infarction (43,676 cases and 128,199 controls) were obtained from the MR-Base platform. In the primary MR analyses, we applied the inverse variance weighted method to evaluate the associations. We performed a sensitivity analysis using weighted median, MR-Egger, weighted mode, simple mode, Mendelian Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and leave-one-out methods. Results: In the primary MR analyses, we found no causal association of genetically predicted AD with ischemic stroke [odds ratio (OR) = 1.00, 95% confidence interval (CI): 0.95–1.06], large artery stroke (OR = 1.02, 95% CI: 0.88–1.17), cardioembolic stroke (OR = 1.06, 95% CI: 0.94–1.18), small vessel stroke (OR = 1.05, 95% CI: 0.94–1.17), coronary heart disease (OR = 1.00, 95% CI: 0.94–1.05), and myocardial infarction (OR = 1.03, 95% CI: 0.98–1.09). The results from the primary MR analyses were supported in sensitivity analyses using the weighted median, weighted mode, simple mode, and MR-Egger methods and multivariable MR analyses adjusting for asthma and several traditional risk factors for ischemic stroke and coronary heart disease. MR-Egger intercepts provided no evidence of directional pleiotropy. The MR-PRESSO and leave-one-out analyses did not indicate any outlier instruments. Conclusion: Our MR study does not support a causal association of genetically predicted AD with ischemic stroke, large artery stroke, cardioembolic stroke, small vessel stroke, coronary heart disease, and myocardial infarction. |
format | Online Article Text |
id | pubmed-9468876 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94688762022-09-14 Investigating the association of atopic dermatitis with ischemic stroke and coronary heart disease: A mendelian randomization study Huang, Jian Gui, Ying Wu, Jing Xie, Yubo Front Genet Genetics Background: Atopic dermatitis (AD) is the most common chronic skin inflammatory disease. Prior observational studies have reported inconsistent results on the association of AD with ischemic stroke and coronary heart disease. In this study, we applied two-sample Mendelian randomization (MR) to evaluate the causal effect of AD on ischemic stroke and coronary heart disease. Methods: Twelve single-nucleotide polymorphisms robustly associated with AD (p < 5 × 10(–8)) were obtained from a genome-wide association study that included 10,788 cases and 30,047 controls by the EArly Genetics and Life course Epidemiology (EAGLE) Consortium (excluding the 23andMe study). The corresponding data for ischemic stroke (34,217 cases and 406,111 controls), large artery stroke (4,373 cases and 406,111 controls), cardioembolic stroke (7,193 cases and 406,111 controls), small vessel stroke (5,386 cases and 192,662 controls), coronary heart disease (122,733 cases and 424,528 controls), and myocardial infarction (43,676 cases and 128,199 controls) were obtained from the MR-Base platform. In the primary MR analyses, we applied the inverse variance weighted method to evaluate the associations. We performed a sensitivity analysis using weighted median, MR-Egger, weighted mode, simple mode, Mendelian Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and leave-one-out methods. Results: In the primary MR analyses, we found no causal association of genetically predicted AD with ischemic stroke [odds ratio (OR) = 1.00, 95% confidence interval (CI): 0.95–1.06], large artery stroke (OR = 1.02, 95% CI: 0.88–1.17), cardioembolic stroke (OR = 1.06, 95% CI: 0.94–1.18), small vessel stroke (OR = 1.05, 95% CI: 0.94–1.17), coronary heart disease (OR = 1.00, 95% CI: 0.94–1.05), and myocardial infarction (OR = 1.03, 95% CI: 0.98–1.09). The results from the primary MR analyses were supported in sensitivity analyses using the weighted median, weighted mode, simple mode, and MR-Egger methods and multivariable MR analyses adjusting for asthma and several traditional risk factors for ischemic stroke and coronary heart disease. MR-Egger intercepts provided no evidence of directional pleiotropy. The MR-PRESSO and leave-one-out analyses did not indicate any outlier instruments. Conclusion: Our MR study does not support a causal association of genetically predicted AD with ischemic stroke, large artery stroke, cardioembolic stroke, small vessel stroke, coronary heart disease, and myocardial infarction. Frontiers Media S.A. 2022-08-30 /pmc/articles/PMC9468876/ /pubmed/36110212 http://dx.doi.org/10.3389/fgene.2022.956850 Text en Copyright © 2022 Huang, Gui, Wu and Xie. 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 Huang, Jian Gui, Ying Wu, Jing Xie, Yubo Investigating the association of atopic dermatitis with ischemic stroke and coronary heart disease: A mendelian randomization study |
title | Investigating the association of atopic dermatitis with ischemic stroke and coronary heart disease: A mendelian randomization study |
title_full | Investigating the association of atopic dermatitis with ischemic stroke and coronary heart disease: A mendelian randomization study |
title_fullStr | Investigating the association of atopic dermatitis with ischemic stroke and coronary heart disease: A mendelian randomization study |
title_full_unstemmed | Investigating the association of atopic dermatitis with ischemic stroke and coronary heart disease: A mendelian randomization study |
title_short | Investigating the association of atopic dermatitis with ischemic stroke and coronary heart disease: A mendelian randomization study |
title_sort | investigating the association of atopic dermatitis with ischemic stroke and coronary heart disease: a mendelian randomization study |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468876/ https://www.ncbi.nlm.nih.gov/pubmed/36110212 http://dx.doi.org/10.3389/fgene.2022.956850 |
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