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Deciphering the host genetic factors conferring susceptibility to severe COVID-19 using exome sequencing

Genes & Immunity volume 25, pages 14–42 (2024)Cite this article

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Abstract

The COVID-19 pandemic remains a significant public health concern despite the new vaccines and therapeutics. The clinical course of acute SARS-CoV-2 infection is highly variable and influenced by several factors related to the virus and the host. Numerous genetic studies, including candidate gene, exome, and genome sequencing studies, genome-wide association studies, and other omics efforts, have proposed various Mendelian and non-Mendelian associations with COVID-19 course. In this study, we conducted whole-exome sequencing on 90 unvaccinated patients from Turkey with no known comorbidities associated with severe COVID-19. Of these patients, 30 had severe, 30 had moderate, and 30 had mild/asymptomatic disease. We identified rare variants in genes associated with SARS-CoV-2 susceptibility and pathogenesis, with an emphasis on genes related to the regulation of inflammation, and discussed these in the context of the clinical course of the patients. In addition, we compared the frequencies of common variants between each group. Even though no variant remained statistically significant after correction for multiple testing, we observed that certain previously associated genes and variants showed significant associations before correction. Our study contributes to the existing literature regarding the genetic susceptibility to SARS-CoV-2. Future studies would be beneficial characterizing the host genetic properties in different populations.

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Fig. 1: Biological process Gene Ontology enrichment analysis of the rare variants.

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Funding

The study was funded by Erciyes University BAP TCD-2021-10936 and received by Munis Dundar.

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Author notes

  1. These authors contributed equally: Kubra Uslu, Firat Ozcelik.

Authors and Affiliations

  1. Department of Medical Genetics, Faculty of Medicine, Erciyes University, Kayseri, Turkey

    Kubra Uslu, Firat Ozcelik, Izem Olcay Sahin, Hilal Akalin, Yusuf Ozkul & Munis Dundar

  2. Department of Biostatistics, Faculty of Medicine, Erciyes University, Kayseri, Turkey

    Gokmen Zararsiz

  3. Drug Application and Research Center (ERFARMA), Erciyes University, Kayseri, Turkey

    Gokmen Zararsiz

  4. Department of Biology, Faculty of Science, Istanbul University, Istanbul, Turkey

    Vahap Eldem

  5. Institutional Data Management and Analytics Units, Erciyes University Rectorate, Kayseri, Turkey

    Ahu Cephe

  6. Division of Intensive Care Medicine, Department of Internal Medicine, Kayseri City Education and Research Hospital, Kayseri, Turkey

    Recep Civan Yuksel, Hilal Sipahioglu & Zuhal Ozer Simsek

  7. Department of Internal Medicine, Kayseri City Education and Research Hospital, Kayseri, Turkey

    Osman Baspinar

  8. Division of Endocrinology and Metabolism, Department of Internal Medicine, Kayseri City Education and Research Hospital, Kayseri, Turkey

    Yasin Simsek

  9. Division of Intensive Care Medicine, Department of Internal Medicine, Faculty of Medicine, Erciyes University, Kayseri, Turkey

    Kursat Gundogan

  10. Department of Chest Diseases, Faculty of Medicine, Erciyes University, Kayseri, Turkey

    Nuri Tutar

  11. Department of Anesthesiology and Reanimation, Faculty of Medicine, Erciyes University, Kayseri, Turkey

    Aynur Karayol Akin

  12. Department of Infectious Diseases, Faculty of Medicine, Erciyes University, Kayseri, Turkey

    Orhan Yildiz

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  1. Kubra Uslu
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Contributions

MD, KU, and FO conceived the study. MD was in charge of overall direction and planning. MD, OY, GZ, NT, KG, KU, and FO designed the study protocol. KU, FO, RCY, HS, ZOS, OB, YS, KG, and AKA provided and gathered patient data. KU and HA contributed to the molecular studies. GZ, VE, AC, and IOS performed the statistical analyses. KU and FO performed the molecular analyses. FO, KU, GZ, and VE wrote the manuscript, MD and YO provided supervision and critical review of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Munis Dundar.

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Uslu, K., Ozcelik, F., Zararsiz, G. et al. Deciphering the host genetic factors conferring susceptibility to severe COVID-19 using exome sequencing. Genes Immun 25, 14–42 (2024). https://doi.org/10.1038/s41435-023-00232-9

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