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Causal association of epigenetic aging and COVID-19 severity and susceptibility: A bidirectional Mendelian randomization study

Observational data from China, the United States, France, and Italy suggest that chronological age is an adverse COVID-19 outcome risk factor, with older patients having a higher severity and mortality rate than younger patients. Most studies have gotten the same view. However, the role of aging in...

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Autores principales: Xu, Wenchang, Zhang, Fengjun, Shi, Yingzhou, Chen, Yuanzhen, Shi, Bin, Yu, Gongchang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9538153/
https://www.ncbi.nlm.nih.gov/pubmed/36213637
http://dx.doi.org/10.3389/fmed.2022.989950
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author Xu, Wenchang
Zhang, Fengjun
Shi, Yingzhou
Chen, Yuanzhen
Shi, Bin
Yu, Gongchang
author_facet Xu, Wenchang
Zhang, Fengjun
Shi, Yingzhou
Chen, Yuanzhen
Shi, Bin
Yu, Gongchang
author_sort Xu, Wenchang
collection PubMed
description Observational data from China, the United States, France, and Italy suggest that chronological age is an adverse COVID-19 outcome risk factor, with older patients having a higher severity and mortality rate than younger patients. Most studies have gotten the same view. However, the role of aging in COVID-19 adverse effects is unclear. To more accurately assess the effect of aging on adverse COVID-19, we conducted this bidirectional Mendelian randomization (MR) study. Epigenetic clocks and telomere length were used as biological indicators of aging. Data on epigenetic age (PhenoAge, GrimAge, Intrinsic HorvathAge, and HannumAge) were derived from an analysis of biological aging based on genome-wide association studies (GWAS) data. The telomere length data are derived from GWAS and the susceptibility and severity data are derived from the COVID-19 Host Genetics Initiative (HGI). Firstly, epigenetic age and telomere length were used as exposures, and following a screen for appropriate instrumental variables, we used random-effects inverse variance weighting (IVW) for the main analysis, and combined it with other analysis methods (e.g., MR Egger, Weighted median, simple mode, Weighted mode) and multiple sensitivity analysis (heterogeneity analysis, horizontal multiplicity analysis, “leave-one-out” analysis). For reducing false-positive rates, Bonferroni corrected significance thresholds were used. A reverse Mendelian randomization analysis was subsequently performed with COVID-19 susceptibility and severity as the exposure. The results of the MR analysis showed no significant differences in susceptibility to aging and COVID-19. It might suggest that aging is not a risk factor for COVID-19 infection (P-values are in the range of 0.05–0.94). According to the results of our analysis, we found that aging was not a risk factor for the increased severity of COVID-19 (P > 0.05). However, severe COVID-19 can cause telomere lengths to become shorter (beta = −0.01; se = 0.01; P = 0.02779). In addition to this, severe COVID-19 infection can slow the acceleration of the epigenetic clock “GrimAge” (beta = −0.24, se = 0.07, P = 0.00122), which may be related to the closely correlation of rs35081325 and COVID-19 severity. Our study provides partial evidence for the causal effects of aging on the susceptibility and severity of COVID-19.
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spelling pubmed-95381532022-10-08 Causal association of epigenetic aging and COVID-19 severity and susceptibility: A bidirectional Mendelian randomization study Xu, Wenchang Zhang, Fengjun Shi, Yingzhou Chen, Yuanzhen Shi, Bin Yu, Gongchang Front Med (Lausanne) Medicine Observational data from China, the United States, France, and Italy suggest that chronological age is an adverse COVID-19 outcome risk factor, with older patients having a higher severity and mortality rate than younger patients. Most studies have gotten the same view. However, the role of aging in COVID-19 adverse effects is unclear. To more accurately assess the effect of aging on adverse COVID-19, we conducted this bidirectional Mendelian randomization (MR) study. Epigenetic clocks and telomere length were used as biological indicators of aging. Data on epigenetic age (PhenoAge, GrimAge, Intrinsic HorvathAge, and HannumAge) were derived from an analysis of biological aging based on genome-wide association studies (GWAS) data. The telomere length data are derived from GWAS and the susceptibility and severity data are derived from the COVID-19 Host Genetics Initiative (HGI). Firstly, epigenetic age and telomere length were used as exposures, and following a screen for appropriate instrumental variables, we used random-effects inverse variance weighting (IVW) for the main analysis, and combined it with other analysis methods (e.g., MR Egger, Weighted median, simple mode, Weighted mode) and multiple sensitivity analysis (heterogeneity analysis, horizontal multiplicity analysis, “leave-one-out” analysis). For reducing false-positive rates, Bonferroni corrected significance thresholds were used. A reverse Mendelian randomization analysis was subsequently performed with COVID-19 susceptibility and severity as the exposure. The results of the MR analysis showed no significant differences in susceptibility to aging and COVID-19. It might suggest that aging is not a risk factor for COVID-19 infection (P-values are in the range of 0.05–0.94). According to the results of our analysis, we found that aging was not a risk factor for the increased severity of COVID-19 (P > 0.05). However, severe COVID-19 can cause telomere lengths to become shorter (beta = −0.01; se = 0.01; P = 0.02779). In addition to this, severe COVID-19 infection can slow the acceleration of the epigenetic clock “GrimAge” (beta = −0.24, se = 0.07, P = 0.00122), which may be related to the closely correlation of rs35081325 and COVID-19 severity. Our study provides partial evidence for the causal effects of aging on the susceptibility and severity of COVID-19. Frontiers Media S.A. 2022-09-23 /pmc/articles/PMC9538153/ /pubmed/36213637 http://dx.doi.org/10.3389/fmed.2022.989950 Text en Copyright © 2022 Xu, Zhang, Shi, Chen, Shi and Yu. 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 Medicine
Xu, Wenchang
Zhang, Fengjun
Shi, Yingzhou
Chen, Yuanzhen
Shi, Bin
Yu, Gongchang
Causal association of epigenetic aging and COVID-19 severity and susceptibility: A bidirectional Mendelian randomization study
title Causal association of epigenetic aging and COVID-19 severity and susceptibility: A bidirectional Mendelian randomization study
title_full Causal association of epigenetic aging and COVID-19 severity and susceptibility: A bidirectional Mendelian randomization study
title_fullStr Causal association of epigenetic aging and COVID-19 severity and susceptibility: A bidirectional Mendelian randomization study
title_full_unstemmed Causal association of epigenetic aging and COVID-19 severity and susceptibility: A bidirectional Mendelian randomization study
title_short Causal association of epigenetic aging and COVID-19 severity and susceptibility: A bidirectional Mendelian randomization study
title_sort causal association of epigenetic aging and covid-19 severity and susceptibility: a bidirectional mendelian randomization study
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9538153/
https://www.ncbi.nlm.nih.gov/pubmed/36213637
http://dx.doi.org/10.3389/fmed.2022.989950
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