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

PLoS One. 2023 Jan 20;18(1):e0279356. doi: 10.1371/journal.pone.0279356. eCollection 2023.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19* / genetics
  • Exons
  • Flavoproteins / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Mutation, Missense
  • Phenotype
  • Phosphoric Monoester Hydrolases / genetics
  • Polymorphism, Single Nucleotide

Substances

  • FIG4 protein, human
  • Flavoproteins
  • Phosphoric Monoester Hydrolases

Grants and funding

This research was partially funded by The National Centre for Research and Development (Narodowe Centrum Badań i Rozwoju) project “Szpitale Jednoimienne/02/2020 "Development of an innovative diagnostic test to assess the course of COVID-19 and post-death complications with the aid of whole-genome analysis", as well as The Medical Research Agency (Agencja Badań Medycznych) project 2020/ABM/COVID19/0022 "A clinical trial in the search for genetic markers responsible for the intensity of the course of the COVID-19 disease, with particular emphasis on patients with accompanying cardiopulmonary diseases”.