Evaluation and limitations of different approaches among COVID-19 fatal cases using whole-exome sequencing data.
COVID-19
Genetic association
Gnomad
Non-invasive prenatal testing
Polymorphisms
SARS-CoV-2
Whole-exome sequencing
Journal
BMC genomics
ISSN: 1471-2164
Titre abrégé: BMC Genomics
Pays: England
ID NLM: 100965258
Informations de publication
Date de publication:
10 Jan 2023
10 Jan 2023
Historique:
received:
28
02
2022
accepted:
15
12
2022
entrez:
10
1
2023
pubmed:
11
1
2023
medline:
13
1
2023
Statut:
epublish
Résumé
COVID-19 caused by the SARS-CoV-2 infection may result in various disease symptoms and severity, ranging from asymptomatic, through mildly symptomatic, up to very severe and even fatal cases. Although environmental, clinical, and social factors play important roles in both susceptibility to the SARS-CoV-2 infection and progress of COVID-19 disease, it is becoming evident that both pathogen and host genetic factors are important too. In this study, we report findings from whole-exome sequencing (WES) of 27 individuals who died due to COVID-19, especially focusing on frequencies of DNA variants in genes previously associated with the SARS-CoV-2 infection and the severity of COVID-19. We selected the risk DNA variants/alleles or target genes using four different approaches: 1) aggregated GWAS results from the GWAS Catalog; 2) selected publications from PubMed; 3) the aggregated results of the Host Genetics Initiative database; and 4) a commercial DNA variant annotation/interpretation tool providing its own knowledgebase. We divided these variants/genes into those reported to influence the susceptibility to the SARS-CoV-2 infection and those influencing the severity of COVID-19. Based on the above, we compared the frequencies of alleles found in the fatal COVID-19 cases to the frequencies identified in two population control datasets (non-Finnish European population from the gnomAD database and genomic frequencies specific for the Slovak population from our own database). When compared to both control population datasets, our analyses indicated a trend of higher frequencies of severe COVID-19 associated risk alleles among fatal COVID-19 cases. This trend reached statistical significance specifically when using the HGI-derived variant list. We also analysed other approaches to WES data evaluation, demonstrating its utility as well as limitations. Although our results proved the likely involvement of host genetic factors pointed out by previous studies looking into severity of COVID-19 disease, careful considerations of the molecular-testing strategies and the evaluated genomic positions may have a strong impact on the utility of genomic testing.
Sections du résumé
BACKGROUND
BACKGROUND
COVID-19 caused by the SARS-CoV-2 infection may result in various disease symptoms and severity, ranging from asymptomatic, through mildly symptomatic, up to very severe and even fatal cases. Although environmental, clinical, and social factors play important roles in both susceptibility to the SARS-CoV-2 infection and progress of COVID-19 disease, it is becoming evident that both pathogen and host genetic factors are important too. In this study, we report findings from whole-exome sequencing (WES) of 27 individuals who died due to COVID-19, especially focusing on frequencies of DNA variants in genes previously associated with the SARS-CoV-2 infection and the severity of COVID-19.
RESULTS
RESULTS
We selected the risk DNA variants/alleles or target genes using four different approaches: 1) aggregated GWAS results from the GWAS Catalog; 2) selected publications from PubMed; 3) the aggregated results of the Host Genetics Initiative database; and 4) a commercial DNA variant annotation/interpretation tool providing its own knowledgebase. We divided these variants/genes into those reported to influence the susceptibility to the SARS-CoV-2 infection and those influencing the severity of COVID-19. Based on the above, we compared the frequencies of alleles found in the fatal COVID-19 cases to the frequencies identified in two population control datasets (non-Finnish European population from the gnomAD database and genomic frequencies specific for the Slovak population from our own database). When compared to both control population datasets, our analyses indicated a trend of higher frequencies of severe COVID-19 associated risk alleles among fatal COVID-19 cases. This trend reached statistical significance specifically when using the HGI-derived variant list. We also analysed other approaches to WES data evaluation, demonstrating its utility as well as limitations.
CONCLUSIONS
CONCLUSIONS
Although our results proved the likely involvement of host genetic factors pointed out by previous studies looking into severity of COVID-19 disease, careful considerations of the molecular-testing strategies and the evaluated genomic positions may have a strong impact on the utility of genomic testing.
Identifiants
pubmed: 36627554
doi: 10.1186/s12864-022-09084-5
pii: 10.1186/s12864-022-09084-5
pmc: PMC9830622
doi:
Substances chimiques
DNA
9007-49-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
12Subventions
Organisme : Pangenomics for personalized clinical management of infected persons based on identified viral genome and human exoma (Code ITMS:313011ATL7), co-financed by the European Regional Development Fund; co financed by the Slovak Research and Development Agency grant PP-COVID-20-051.
ID : PP-COVID-20-051
Organisme : Pangenomics for personalized clinical management of infected persons based on identified viral genome and human exoma (Code ITMS:313011ATL7), co-financed by the European Regional Development Fund; co financed by the Slovak Research and Development Agency grant PP-COVID-20-051.
ID : PP-COVID-20-051
Organisme : Pangenomics for personalized clinical management of infected persons based on identified viral genome and human exoma (Code ITMS:313011ATL7), co-financed by the European Regional Development Fund; co financed by the Slovak Research and Development Agency grant PP-COVID-20-051.
ID : PP-COVID-20-051
Informations de copyright
© 2023. The Author(s).
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