Canadian COVID-19 host genetics cohort replicates known severity associations

Canadian COVID-19 host genetics cohort replicates known severity associations

The HostSeq initiative recruited 10,059 Canadians infected with SARS-CoV-2 between March 2020 and March 2023, obtained clinical information on their disease experience and whole genome sequenced (WGS) their DNA. We analyzed the WGS data for genetic contributors to severe COVID-19 (considering 3,499...

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Published in:PLoS genetics Vol. 20; no. 3; p. e1011192
Main Authors: Garg, Elika, Arguello-Pascualli, Paola, Vishnyakova, Olga, Halevy, Anat R, Yoo, Samantha, Brooks, Jennifer D, Bull, Shelley B, Gagnon, France, Greenwood, Celia M T, Hung, Rayjean J, Lawless, Jerald F, Lerner-Ellis, Jordan, Dennis, Jessica K, Abraham, Rohan J S, Garant, Jean-Michel, Thiruvahindrapuram, Bhooma, Jones, Steven J M, Strug, Lisa J, Paterson, Andrew D, Sun, Lei, Elliott, Lloyd T
Format: Journal Article
Language:English
Published: United States Public Library of Science 22-03-2024
Subjects:
Analysis
Biology and Life Sciences
Chromosome 3
Chromosome 6
COVID-19
CRISPR
Data processing
Genes
Genetic aspects
Genetics
Genomes
Genomics
Haplotypes
Health aspects
Hospitalization
Host-virus relationships
Infections
Infectious diseases
Interferon
Males
Medicine and Health Sciences
Nucleotide sequence
Pandemics
Physical Sciences
Quality control
Research and Analysis Methods
Sample size
Severe acute respiratory syndrome coronavirus 2
Canada
United States
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Summary:The HostSeq initiative recruited 10,059 Canadians infected with SARS-CoV-2 between March 2020 and March 2023, obtained clinical information on their disease experience and whole genome sequenced (WGS) their DNA. We analyzed the WGS data for genetic contributors to severe COVID-19 (considering 3,499 hospitalized cases and 4,975 non-hospitalized after quality control). We investigated the evidence for replication of loci reported by the International Host Genetics Initiative (HGI); analyzed the X chromosome; conducted rare variant gene-based analysis and polygenic risk score testing. Population stratification was adjusted for using meta-analysis across ancestry groups. We replicated two loci identified by the HGI for COVID-19 severity: the LZTFL1/SLC6A20 locus on chromosome 3 and the FOXP4 locus on chromosome 6 (the latter with a variant significant at P < 5E-8). We found novel significant associations with MRAS and WDR89 in gene-based analyses, and constructed a polygenic risk score that explained 1.01% of the variance in severe COVID-19. This study provides independent evidence confirming the robustness of previously identified COVID-19 severity loci by the HGI and identifies novel genes for further investigation.
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https://www.cgen.ca/hostseq-contributing-studies-implementation-committee
The authors have declared that no competing interests exist.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1011192