Genome-wide association study between SARS-CoV-2 single nucleotide polymorphisms and virus copies during infections.

Autor: Li K; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America.; Public Health Modeling Unit, Yale School of Public Health, New Haven, Connecticut, United States of America., Chaguza C; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America.; Public Health Modeling Unit, Yale School of Public Health, New Haven, Connecticut, United States of America., Stamp J; Center for Computational Molecular Biology, Brown University, Providence, Rhode Island, United States of America., Chew YT; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America.; Public Health Modeling Unit, Yale School of Public Health, New Haven, Connecticut, United States of America., Chen NFG; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America., Ferguson D; Department of Laboratory Medicine, Yale School of Medicine, New Haven, Connecticut, United States of America.; Yale School of Medicine Biorepository, Yale University, New Haven, Connecticut, United States of America., Pandya S; Department of Laboratory Medicine, Yale School of Medicine, New Haven, Connecticut, United States of America.; Yale School of Medicine Biorepository, Yale University, New Haven, Connecticut, United States of America., Kerantzas N; Department of Laboratory Medicine, Yale School of Medicine, New Haven, Connecticut, United States of America.; Yale School of Medicine Biorepository, Yale University, New Haven, Connecticut, United States of America., Schulz W; Department of Laboratory Medicine, Yale School of Medicine, New Haven, Connecticut, United States of America.; Yale School of Medicine Biorepository, Yale University, New Haven, Connecticut, United States of America., Hahn AM; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America., Ogbunugafor CB; Public Health Modeling Unit, Yale School of Public Health, New Haven, Connecticut, United States of America.; Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut, United States of America.; Santa Fe Institute, Santa Fe, New Mexico, United States of America., Pitzer VE; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America.; Public Health Modeling Unit, Yale School of Public Health, New Haven, Connecticut, United States of America., Crawford L; Center for Computational Molecular Biology, Brown University, Providence, Rhode Island, United States of America.; Department of Biostatistics, Brown University, Providence, Rhode Island, United States of America.; Microsoft Research, Cambridge, Massachusetts, United States of America., Weinberger DM; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America.; Public Health Modeling Unit, Yale School of Public Health, New Haven, Connecticut, United States of America., Grubaugh ND; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America.; Public Health Modeling Unit, Yale School of Public Health, New Haven, Connecticut, United States of America.; Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut, United States of America.
Jazyk: angličtina
Zdroj: PLoS computational biology [PLoS Comput Biol] 2024 Sep 17; Vol. 20 (9), pp. e1012469. Date of Electronic Publication: 2024 Sep 17 (Print Publication: 2024).
DOI: 10.1371/journal.pcbi.1012469
Abstrakt: Significant variations have been observed in viral copies generated during SARS-CoV-2 infections. However, the factors that impact viral copies and infection dynamics are not fully understood, and may be inherently dependent upon different viral and host factors. Here, we conducted virus whole genome sequencing and measured viral copies using RT-qPCR from 9,902 SARS-CoV-2 infections over a 2-year period to examine the impact of virus genetic variation on changes in viral copies adjusted for host age and vaccination status. Using a genome-wide association study (GWAS) approach, we identified multiple single-nucleotide polymorphisms (SNPs) corresponding to amino acid changes in the SARS-CoV-2 genome associated with variations in viral copies. We further applied a marginal epistasis test to detect interactions among SNPs and identified multiple pairs of substitutions located in the spike gene that have non-linear effects on viral copies. We also analyzed the temporal patterns and found that SNPs associated with increased viral copies were predominantly observed in Delta and Omicron BA.2/BA.4/BA.5/XBB infections, whereas those associated with decreased viral copies were only observed in infections with Omicron BA.1 variants. Our work showcases how GWAS can be a useful tool for probing phenotypes related to SNPs in viral genomes that are worth further exploration. We argue that this approach can be used more broadly across pathogens to characterize emerging variants and monitor therapeutic interventions.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: NDG is a paid consultant for BioNTech, DMW has received consulting fees from Pfizer, Merck, and GSK, unrelated to this manuscript, and has been PI on research grants from Pfizer and Merck to Yale, unrelated to this manuscript.
(Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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