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Article

Beyond GWAS—Could Genetic Differentiation within the Allograft Rejection Pathway Shape Natural Immunity to COVID-19?

1
Biostatistics Group, Department of Genetics, Wrocław University of Environmental and Life Sciences, 51-631 Wroclaw, Poland
2
Department of Cattle Breeding, National Research Institute of Animal Production, Krakowska 1, 32-083 Balice, Poland
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Central Clinical Hospital of Ministry of the Interior and Administration in Warsaw, 02-507 Warsaw, Poland
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Department of Haematology, Transplantation and Internal Medicine, University Clinical Centre of the Medical University of Warsaw, 02-091 Warsaw, Poland
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MNM Diagnostics, Małe Garbary 9, 61-756 Poznan, Poland
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Department of Neurology and Neurophysiology, University of Zurich, Balgrist University Hospital, 8008 Zurich, Switzerland
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Department of Infectious Diseases, Medical University of Lublin, 20-059 Lublin, Poland
*
Authors to whom correspondence should be addressed.
Academic Editors: Bartosz Jan Płachno, Petr Babula and Małgorzata Kotula-Balak
Int. J. Mol. Sci. 2022, 23(11), 6272; https://doi.org/10.3390/ijms23116272
Received: 19 April 2022 / Revised: 26 May 2022 / Accepted: 30 May 2022 / Published: 3 June 2022
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 (p = 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. View Full-Text
Keywords: KEGG pathways; allograft rejection; GWAS; COVID-19 infection; susceptibility; resistance; genetic variants; single nucleotide polymorphism; whole genome sequencing; immunisation KEGG pathways; allograft rejection; GWAS; COVID-19 infection; susceptibility; resistance; genetic variants; single nucleotide polymorphism; whole genome sequencing; immunisation
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MDPI and ACS Style

Szyda, J.; Dobosz, P.; Stojak, J.; Sypniewski, M.; Suchocki, T.; Kotlarz, K.; Mroczek, M.; Stępień, M.; Słomian, D.; Butkiewicz, S.; Sztromwasser, P.; Liu, J.; Król, Z.J. Beyond GWAS—Could Genetic Differentiation within the Allograft Rejection Pathway Shape Natural Immunity to COVID-19? Int. J. Mol. Sci. 2022, 23, 6272. https://doi.org/10.3390/ijms23116272

AMA Style

Szyda J, Dobosz P, Stojak J, Sypniewski M, Suchocki T, Kotlarz K, Mroczek M, Stępień M, Słomian D, Butkiewicz S, Sztromwasser P, Liu J, Król ZJ. Beyond GWAS—Could Genetic Differentiation within the Allograft Rejection Pathway Shape Natural Immunity to COVID-19? International Journal of Molecular Sciences. 2022; 23(11):6272. https://doi.org/10.3390/ijms23116272

Chicago/Turabian Style

Szyda, Joanna, Paula Dobosz, Joanna Stojak, Mateusz Sypniewski, Tomasz Suchocki, Krzysztof Kotlarz, Magdalena Mroczek, Maria Stępień, Dawid Słomian, Sławomir Butkiewicz, Paweł Sztromwasser, Jakub Liu, and Zbigniew J. Król. 2022. "Beyond GWAS—Could Genetic Differentiation within the Allograft Rejection Pathway Shape Natural Immunity to COVID-19?" International Journal of Molecular Sciences 23, no. 11: 6272. https://doi.org/10.3390/ijms23116272

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