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Shared genetic mechanism between type 2 diabetes and COVID-19 using pathway-based association analysis

Recent studies have shown that, compared with healthy individuals, patients with type 2 diabetes (T2D) suffer a higher severity and mortality of COVID-19. When infected with this retrovirus, patients with T2D are more likely to face severe complications from cytokine storms and be admitted to high-d...

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Autores principales: Wu, Kevin Chun Hei, He, Qian, Bennett, Adam N., Li, Jie, Chan, Kei Hang Katie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9724785/
https://www.ncbi.nlm.nih.gov/pubmed/36482905
http://dx.doi.org/10.3389/fgene.2022.1063519
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author Wu, Kevin Chun Hei
He, Qian
Bennett, Adam N.
Li, Jie
Chan, Kei Hang Katie
author_facet Wu, Kevin Chun Hei
He, Qian
Bennett, Adam N.
Li, Jie
Chan, Kei Hang Katie
author_sort Wu, Kevin Chun Hei
collection PubMed
description Recent studies have shown that, compared with healthy individuals, patients with type 2 diabetes (T2D) suffer a higher severity and mortality of COVID-19. When infected with this retrovirus, patients with T2D are more likely to face severe complications from cytokine storms and be admitted to high-dependency or intensive care units. Some COVID-19 patients are known to suffer from various forms of acute respiratory distress syndrome and have a higher mortality risk due to extreme activation of inflammatory cascades. Using a conditional false discovery rate statistical framework, an independent genome-wide association study data on individuals presenting with T2D (N = 62,892) and COVID-19 (N = 38,984) were analysed. Genome-wide association study data from 2,343,084 participants were analysed and a significant positive genetic correlation between T2D and COVID-19 was observed (T2D: r for genetic = 0.1511, p-value = 0.01). Overall, 2 SNPs (rs505922 and rs3924604) shared in common between T2D and COVID-19 were identified. Functional analyses indicated that the overlapping loci annotated into the ABO and NUS1 genes might be implicated in several key metabolic pathways. A pathway association analysis identified two common pathways within T2D and COVID-19 pathogenesis, including chemokines and their respective receptors. The gene identified from the pathway analysis (CCR2) was also found to be highly expressed in blood tissue via the GTEx database. To conclude, this study reveals that certain chemokines and their receptors, which are directly involved in the genesis of cytokine storms, may lead to exacerbated hyperinflammation in T2D patients infected by COVID-19.
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spelling pubmed-97247852022-12-07 Shared genetic mechanism between type 2 diabetes and COVID-19 using pathway-based association analysis Wu, Kevin Chun Hei He, Qian Bennett, Adam N. Li, Jie Chan, Kei Hang Katie Front Genet Genetics Recent studies have shown that, compared with healthy individuals, patients with type 2 diabetes (T2D) suffer a higher severity and mortality of COVID-19. When infected with this retrovirus, patients with T2D are more likely to face severe complications from cytokine storms and be admitted to high-dependency or intensive care units. Some COVID-19 patients are known to suffer from various forms of acute respiratory distress syndrome and have a higher mortality risk due to extreme activation of inflammatory cascades. Using a conditional false discovery rate statistical framework, an independent genome-wide association study data on individuals presenting with T2D (N = 62,892) and COVID-19 (N = 38,984) were analysed. Genome-wide association study data from 2,343,084 participants were analysed and a significant positive genetic correlation between T2D and COVID-19 was observed (T2D: r for genetic = 0.1511, p-value = 0.01). Overall, 2 SNPs (rs505922 and rs3924604) shared in common between T2D and COVID-19 were identified. Functional analyses indicated that the overlapping loci annotated into the ABO and NUS1 genes might be implicated in several key metabolic pathways. A pathway association analysis identified two common pathways within T2D and COVID-19 pathogenesis, including chemokines and their respective receptors. The gene identified from the pathway analysis (CCR2) was also found to be highly expressed in blood tissue via the GTEx database. To conclude, this study reveals that certain chemokines and their receptors, which are directly involved in the genesis of cytokine storms, may lead to exacerbated hyperinflammation in T2D patients infected by COVID-19. Frontiers Media S.A. 2022-11-22 /pmc/articles/PMC9724785/ /pubmed/36482905 http://dx.doi.org/10.3389/fgene.2022.1063519 Text en Copyright © 2022 Wu, He, Bennett, Li and Chan. 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
Wu, Kevin Chun Hei
He, Qian
Bennett, Adam N.
Li, Jie
Chan, Kei Hang Katie
Shared genetic mechanism between type 2 diabetes and COVID-19 using pathway-based association analysis
title Shared genetic mechanism between type 2 diabetes and COVID-19 using pathway-based association analysis
title_full Shared genetic mechanism between type 2 diabetes and COVID-19 using pathway-based association analysis
title_fullStr Shared genetic mechanism between type 2 diabetes and COVID-19 using pathway-based association analysis
title_full_unstemmed Shared genetic mechanism between type 2 diabetes and COVID-19 using pathway-based association analysis
title_short Shared genetic mechanism between type 2 diabetes and COVID-19 using pathway-based association analysis
title_sort shared genetic mechanism between type 2 diabetes and covid-19 using pathway-based association analysis
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9724785/
https://www.ncbi.nlm.nih.gov/pubmed/36482905
http://dx.doi.org/10.3389/fgene.2022.1063519
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