In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 18, No. 11 ( 2022-11-3), p. e1010367-
Abstract:
Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10 -7 ). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1010367
DOI:
10.1371/journal.pgen.1010367.g001
DOI:
10.1371/journal.pgen.1010367.g002
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10.1371/journal.pgen.1010367.g003
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10.1371/journal.pgen.1010367.g004
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10.1371/journal.pgen.1010367.g005
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10.1371/journal.pgen.1010367.t001
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10.1371/journal.pgen.1010367.t002
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10.1371/journal.pgen.1010367.t003
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10.1371/journal.pgen.1010367.s001
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10.1371/journal.pgen.1010367.s002
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10.1371/journal.pgen.1010367.s003
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10.1371/journal.pgen.1010367.s013
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10.1371/journal.pgen.1010367.s014
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10.1371/journal.pgen.1010367.s015
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10.1371/journal.pgen.1010367.s016
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10.1371/journal.pgen.1010367.s017
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10.1371/journal.pgen.1010367.s018
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10.1371/journal.pgen.1010367.s019
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10.1371/journal.pgen.1010367.s020
DOI:
10.1371/journal.pgen.1010367.s021
DOI:
10.1371/journal.pgen.1010367.s022
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2186725-2
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