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Telomere Length and COVID-19 Outcomes: A Two-Sample Bidirectional Mendelian Randomization Study

Observational studies have found a relationship between directly measured short leukocyte telomere length (LTL) and severe coronavirus disease 19 (COVID-19). We investigated the causal association between genetically predicted LTL and COVID-19 susceptibility or severity. A previous genome-wide assoc...

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Autores principales: Jiang, Li, Tang, Bei-sha, Guo, Ji-feng, Li, Jin-chen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168682/
https://www.ncbi.nlm.nih.gov/pubmed/35677559
http://dx.doi.org/10.3389/fgene.2022.805903
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author Jiang, Li
Tang, Bei-sha
Guo, Ji-feng
Li, Jin-chen
author_facet Jiang, Li
Tang, Bei-sha
Guo, Ji-feng
Li, Jin-chen
author_sort Jiang, Li
collection PubMed
description Observational studies have found a relationship between directly measured short leukocyte telomere length (LTL) and severe coronavirus disease 19 (COVID-19). We investigated the causal association between genetically predicted LTL and COVID-19 susceptibility or severity. A previous genome-wide association study (GWAS) of 78,592 European-ancestry participants identified single nucleotidepolymorphisms (SNPs) that can be utilized to genetically predict LTL. Summary-level data for COVID-19 outcomes were analyzed from the COVID-19 Host Genetics Initiative. A two-sample bidirectional Mendelian randomization (MR) study was designed to evaluate these causal relationships. Using an inverse-weighted MR analysis and population-based controls, genetically predicted LTL did not reveal any significant association with COVID-19 susceptibility (odds ratio (OR): 0.94; 95% CI: 0.85–1.04; p = 0.202) or severity (OR: 0.85; 95% CI: 0.70–1.03; p = 0.099). Similar results were found for five other definitions of cases/controls and/or COVID-19 outcomes. Six additional MR methods and sensitivity analyses were conducted after removing variants with potential horizontal pleiotropy and including variants at a liberal significance level, which produced similar results. Using SNPs identified for the prediction of LTL from another GWAS study, we found a non-significant association for COVID-19 susceptibility or severity with narrower CIs toward the null hypothesis. No proof of genetically predicted COVID-19 phenotypes remained causally associated with genetically predicted LTL, and the null association was consistent with a lack of significant genetic correlation. Genetic evidence does not support shorter LTL as a causal risk factor for COVID-19 susceptibility or severity.
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spelling pubmed-91686822022-06-07 Telomere Length and COVID-19 Outcomes: A Two-Sample Bidirectional Mendelian Randomization Study Jiang, Li Tang, Bei-sha Guo, Ji-feng Li, Jin-chen Front Genet Genetics Observational studies have found a relationship between directly measured short leukocyte telomere length (LTL) and severe coronavirus disease 19 (COVID-19). We investigated the causal association between genetically predicted LTL and COVID-19 susceptibility or severity. A previous genome-wide association study (GWAS) of 78,592 European-ancestry participants identified single nucleotidepolymorphisms (SNPs) that can be utilized to genetically predict LTL. Summary-level data for COVID-19 outcomes were analyzed from the COVID-19 Host Genetics Initiative. A two-sample bidirectional Mendelian randomization (MR) study was designed to evaluate these causal relationships. Using an inverse-weighted MR analysis and population-based controls, genetically predicted LTL did not reveal any significant association with COVID-19 susceptibility (odds ratio (OR): 0.94; 95% CI: 0.85–1.04; p = 0.202) or severity (OR: 0.85; 95% CI: 0.70–1.03; p = 0.099). Similar results were found for five other definitions of cases/controls and/or COVID-19 outcomes. Six additional MR methods and sensitivity analyses were conducted after removing variants with potential horizontal pleiotropy and including variants at a liberal significance level, which produced similar results. Using SNPs identified for the prediction of LTL from another GWAS study, we found a non-significant association for COVID-19 susceptibility or severity with narrower CIs toward the null hypothesis. No proof of genetically predicted COVID-19 phenotypes remained causally associated with genetically predicted LTL, and the null association was consistent with a lack of significant genetic correlation. Genetic evidence does not support shorter LTL as a causal risk factor for COVID-19 susceptibility or severity. Frontiers Media S.A. 2022-05-23 /pmc/articles/PMC9168682/ /pubmed/35677559 http://dx.doi.org/10.3389/fgene.2022.805903 Text en Copyright © 2022 Jiang, Tang, Guo and Li. 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
Jiang, Li
Tang, Bei-sha
Guo, Ji-feng
Li, Jin-chen
Telomere Length and COVID-19 Outcomes: A Two-Sample Bidirectional Mendelian Randomization Study
title Telomere Length and COVID-19 Outcomes: A Two-Sample Bidirectional Mendelian Randomization Study
title_full Telomere Length and COVID-19 Outcomes: A Two-Sample Bidirectional Mendelian Randomization Study
title_fullStr Telomere Length and COVID-19 Outcomes: A Two-Sample Bidirectional Mendelian Randomization Study
title_full_unstemmed Telomere Length and COVID-19 Outcomes: A Two-Sample Bidirectional Mendelian Randomization Study
title_short Telomere Length and COVID-19 Outcomes: A Two-Sample Bidirectional Mendelian Randomization Study
title_sort telomere length and covid-19 outcomes: a two-sample bidirectional mendelian randomization study
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168682/
https://www.ncbi.nlm.nih.gov/pubmed/35677559
http://dx.doi.org/10.3389/fgene.2022.805903
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