Beyond GWAS—Could Genetic Differentiation within the Allograft Rejection Pathway Shape Natural Immunity to COVID-19?
COVID-19 infections pose a serious global health concern so it is crucial to identify the biomarkers for the susceptibility to and resistance against this disease that could help in a rapid risk assessment and reliable decisions being made on patients’ treatment and their potential hospitalisation....
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/11/6272 |
| _version_ | 1797493015205380096 |
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| author | Joanna Szyda Paula Dobosz Joanna Stojak Mateusz Sypniewski Tomasz Suchocki Krzysztof Kotlarz Magdalena Mroczek Maria Stępień Dawid Słomian Sławomir Butkiewicz Paweł Sztromwasser Jakub Liu Zbigniew J. Król |
| author_facet | Joanna Szyda Paula Dobosz Joanna Stojak Mateusz Sypniewski Tomasz Suchocki Krzysztof Kotlarz Magdalena Mroczek Maria Stępień Dawid Słomian Sławomir Butkiewicz Paweł Sztromwasser Jakub Liu Zbigniew J. Król |
| author_sort | Joanna Szyda |
| collection | DOAJ |
| description | COVID-19 infections pose a serious global health concern so it is crucial to identify the biomarkers for the susceptibility to and resistance against this disease that could help in a rapid risk assessment and reliable decisions being made on patients’ treatment and their potential hospitalisation. Several studies investigated the factors associated with severe COVID-19 outcomes that can be either environmental, population based, or genetic. It was demonstrated that the genetics of the host plays an important role in the various immune responses and, therefore, there are different clinical presentations of COVID-19 infection. In this study, we aimed to use variant descriptive statistics from GWAS (Genome-Wide Association Study) and variant genomic annotations to identify metabolic pathways that are associated with a severe COVID-19 infection as well as pathways related to resistance to COVID-19. For this purpose, we applied a custom-designed mixed linear model implemented into custom-written software. Our analysis of more than 12.5 million SNPs did not indicate any pathway that was significant for a severe COVID-19 infection. However, the Allograft rejection pathway (hsa05330) was significant (<i>p</i> = 0.01087) for resistance to the infection. The majority of the 27 SNP marking genes constituting the Allograft rejection pathway were located on chromosome 6 (19 SNPs) and the remainder were mapped to chromosomes 2, 3, 10, 12, 20, and X. This pathway comprises several immune system components crucial for the self versus non-self recognition, but also the components of antiviral immunity. Our study demonstrated that not only single variants are important for resistance to COVID-19, but also the cumulative impact of several SNPs within the same pathway matters. |
| first_indexed | 2024-03-10T01:13:55Z |
| format | Article |
| id | doaj.art-2a92c1d194bf4ff7bcc8fa74021ba257 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:13:55Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2a92c1d194bf4ff7bcc8fa74021ba2572023-11-23T14:12:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012311627210.3390/ijms23116272Beyond GWAS—Could Genetic Differentiation within the Allograft Rejection Pathway Shape Natural Immunity to COVID-19?Joanna Szyda0Paula Dobosz1Joanna Stojak2Mateusz Sypniewski3Tomasz Suchocki4Krzysztof Kotlarz5Magdalena Mroczek6Maria Stępień7Dawid Słomian8Sławomir Butkiewicz9Paweł Sztromwasser10Jakub Liu11Zbigniew J. Król12Biostatistics Group, Department of Genetics, Wrocław University of Environmental and Life Sciences, 51-631 Wroclaw, PolandCentral Clinical Hospital of Ministry of the Interior and Administration in Warsaw, 02-507 Warsaw, PolandCentral Clinical Hospital of Ministry of the Interior and Administration in Warsaw, 02-507 Warsaw, PolandMNM Diagnostics, Małe Garbary 9, 61-756 Poznan, PolandBiostatistics Group, Department of Genetics, Wrocław University of Environmental and Life Sciences, 51-631 Wroclaw, PolandBiostatistics Group, Department of Genetics, Wrocław University of Environmental and Life Sciences, 51-631 Wroclaw, PolandDepartment of Neurology and Neurophysiology, University of Zurich, Balgrist University Hospital, 8008 Zurich, SwitzerlandDepartment of Infectious Diseases, Medical University of Lublin, 20-059 Lublin, PolandDepartment of Cattle Breeding, National Research Institute of Animal Production, Krakowska 1, 32-083 Balice, PolandCentral Clinical Hospital of Ministry of the Interior and Administration in Warsaw, 02-507 Warsaw, PolandMNM Diagnostics, Małe Garbary 9, 61-756 Poznan, PolandBiostatistics Group, Department of Genetics, Wrocław University of Environmental and Life Sciences, 51-631 Wroclaw, PolandCentral Clinical Hospital of Ministry of the Interior and Administration in Warsaw, 02-507 Warsaw, PolandCOVID-19 infections pose a serious global health concern so it is crucial to identify the biomarkers for the susceptibility to and resistance against this disease that could help in a rapid risk assessment and reliable decisions being made on patients’ treatment and their potential hospitalisation. Several studies investigated the factors associated with severe COVID-19 outcomes that can be either environmental, population based, or genetic. It was demonstrated that the genetics of the host plays an important role in the various immune responses and, therefore, there are different clinical presentations of COVID-19 infection. In this study, we aimed to use variant descriptive statistics from GWAS (Genome-Wide Association Study) and variant genomic annotations to identify metabolic pathways that are associated with a severe COVID-19 infection as well as pathways related to resistance to COVID-19. For this purpose, we applied a custom-designed mixed linear model implemented into custom-written software. Our analysis of more than 12.5 million SNPs did not indicate any pathway that was significant for a severe COVID-19 infection. However, the Allograft rejection pathway (hsa05330) was significant (<i>p</i> = 0.01087) for resistance to the infection. The majority of the 27 SNP marking genes constituting the Allograft rejection pathway were located on chromosome 6 (19 SNPs) and the remainder were mapped to chromosomes 2, 3, 10, 12, 20, and X. This pathway comprises several immune system components crucial for the self versus non-self recognition, but also the components of antiviral immunity. Our study demonstrated that not only single variants are important for resistance to COVID-19, but also the cumulative impact of several SNPs within the same pathway matters.https://www.mdpi.com/1422-0067/23/11/6272KEGG pathwaysallograft rejectionGWASCOVID-19 infectionsusceptibilityresistance |
| spellingShingle | Joanna Szyda Paula Dobosz Joanna Stojak Mateusz Sypniewski Tomasz Suchocki Krzysztof Kotlarz Magdalena Mroczek Maria Stępień Dawid Słomian Sławomir Butkiewicz Paweł Sztromwasser Jakub Liu Zbigniew J. Król Beyond GWAS—Could Genetic Differentiation within the Allograft Rejection Pathway Shape Natural Immunity to COVID-19? International Journal of Molecular Sciences KEGG pathways allograft rejection GWAS COVID-19 infection susceptibility resistance |
| title | Beyond GWAS—Could Genetic Differentiation within the Allograft Rejection Pathway Shape Natural Immunity to COVID-19? |
| title_full | Beyond GWAS—Could Genetic Differentiation within the Allograft Rejection Pathway Shape Natural Immunity to COVID-19? |
| title_fullStr | Beyond GWAS—Could Genetic Differentiation within the Allograft Rejection Pathway Shape Natural Immunity to COVID-19? |
| title_full_unstemmed | Beyond GWAS—Could Genetic Differentiation within the Allograft Rejection Pathway Shape Natural Immunity to COVID-19? |
| title_short | Beyond GWAS—Could Genetic Differentiation within the Allograft Rejection Pathway Shape Natural Immunity to COVID-19? |
| title_sort | beyond gwas could genetic differentiation within the allograft rejection pathway shape natural immunity to covid 19 |
| topic | KEGG pathways allograft rejection GWAS COVID-19 infection susceptibility resistance |
| url | https://www.mdpi.com/1422-0067/23/11/6272 |
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