Better safe than sorry—Whole-genome sequencing indicates that missense variants are significant in susceptibility to COVID-19

• DOI: 10.1371/journal.pone.0279356
• Publication Date: 2023-01-20T18:56:50Z
• Authors: Dawid Słomian; Joanna Szyda; Paula Dobosz; Joanna Stojak; Anna Michalska-Fo...; Mateusz Sypniewski; Jakub Liu; Krzysztof Kotlarz; Tomasz Suchocki; Magdalena Mroczek; Maria Stępień; Paweł Sztromwasser; Zbigniew J. Król
• Keywords: 0301 basic medicine; Flavoproteins; Science; Q; R; Mutation, Missense; COVID-19; Exons; Polymorphism, Single Nucleotide; Phosphoric Monoester Hydrolases; 3. Good health; 03 medical and health sciences; Phenotype; Medicine; Humans; Genetic Predisposition to Disease; Research Article; Genome-Wide Association Study

Undoubtedly, genetic factors play an important role in susceptibility and resistance to COVID-19. In this study, we conducted the GWAS analysis. Out of 15,489,173 SNPs, we identified 18,191 significant SNPs for severe and 11,799 SNPs for resistant phenotype, showing that a great number of loci were significant in different COVID-19 representations. The majority of variants were synonymous (60.56% for severe, 58.46% for resistant phenotype) or located in introns (55.77% for severe, 59.83% for resistant phenotype). We identified the most significant SNPs for a severe outcome (in AJAP1 intron) and for COVID resistance (in FIG4 intron). We found no missense variants with a potential causal function on resistance to COVID-19; however, two missense variants were determined as significant a severe phenotype (in PM20D1 and LRP4 exons). None of the aforementioned SNPs and missense variants found in this study have been previously associated with COVID-19.