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Identification of Causal Genes of COVID-19 Using the SMR Method

Since the first report of COVID-19 in December 2019, more than 100 million people have been infected with SARS-CoV-2. Despite ongoing research, there is still limited knowledge about the genetic causes of COVID-19. To resolve this problem, we applied the SMR method to analyze the genes involved in C...

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Autores principales: Zong, Yan, Li, Xiaofei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287881/
https://www.ncbi.nlm.nih.gov/pubmed/34290742
http://dx.doi.org/10.3389/fgene.2021.690349
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author Zong, Yan
Li, Xiaofei
author_facet Zong, Yan
Li, Xiaofei
author_sort Zong, Yan
collection PubMed
description Since the first report of COVID-19 in December 2019, more than 100 million people have been infected with SARS-CoV-2. Despite ongoing research, there is still limited knowledge about the genetic causes of COVID-19. To resolve this problem, we applied the SMR method to analyze the genes involved in COVID-19 pathogenesis by the integration of multiple omics data. Here, we assessed the SNPs associated with COVID-19 risk from the GWAS data of Spanish and Italian patients and lung eQTL data from the GTEx project. Then, GWAS and eQTL data were integrated by summary-data-based (SMR) methods using SNPs as instrumental variables (IVs). As a result, six protein-coding and five non-protein-coding genes regulated by nine SNPs were identified as significant risk factors for COVID-19. Functional analysis of these genes showed that UQCRH participates in cardiac muscle contraction, PPA2 is closely related to sudden cardiac failure (SCD), and OGT, as the interacting gene partner of PANO1, is associated with neurological disease. Observational studies show that myocardial damage, SCD, and neurological disease often occur in COVID-19 patients. Thus, our findings provide a potential molecular mechanism for understanding the complications of COVID-19.
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spelling pubmed-82878812021-07-20 Identification of Causal Genes of COVID-19 Using the SMR Method Zong, Yan Li, Xiaofei Front Genet Genetics Since the first report of COVID-19 in December 2019, more than 100 million people have been infected with SARS-CoV-2. Despite ongoing research, there is still limited knowledge about the genetic causes of COVID-19. To resolve this problem, we applied the SMR method to analyze the genes involved in COVID-19 pathogenesis by the integration of multiple omics data. Here, we assessed the SNPs associated with COVID-19 risk from the GWAS data of Spanish and Italian patients and lung eQTL data from the GTEx project. Then, GWAS and eQTL data were integrated by summary-data-based (SMR) methods using SNPs as instrumental variables (IVs). As a result, six protein-coding and five non-protein-coding genes regulated by nine SNPs were identified as significant risk factors for COVID-19. Functional analysis of these genes showed that UQCRH participates in cardiac muscle contraction, PPA2 is closely related to sudden cardiac failure (SCD), and OGT, as the interacting gene partner of PANO1, is associated with neurological disease. Observational studies show that myocardial damage, SCD, and neurological disease often occur in COVID-19 patients. Thus, our findings provide a potential molecular mechanism for understanding the complications of COVID-19. Frontiers Media S.A. 2021-07-05 /pmc/articles/PMC8287881/ /pubmed/34290742 http://dx.doi.org/10.3389/fgene.2021.690349 Text en Copyright © 2021 Zong 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
Zong, Yan
Li, Xiaofei
Identification of Causal Genes of COVID-19 Using the SMR Method
title Identification of Causal Genes of COVID-19 Using the SMR Method
title_full Identification of Causal Genes of COVID-19 Using the SMR Method
title_fullStr Identification of Causal Genes of COVID-19 Using the SMR Method
title_full_unstemmed Identification of Causal Genes of COVID-19 Using the SMR Method
title_short Identification of Causal Genes of COVID-19 Using the SMR Method
title_sort identification of causal genes of covid-19 using the smr method
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287881/
https://www.ncbi.nlm.nih.gov/pubmed/34290742
http://dx.doi.org/10.3389/fgene.2021.690349
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