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SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicit...

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Autores principales: D’Antonio, Matteo, Nguyen, Jennifer P., Arthur, Timothy D., Matsui, Hiroko, D’Antonio-Chronowska, Agnieszka, Frazer, Kelly A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Author(s). 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563343/
https://www.ncbi.nlm.nih.gov/pubmed/34762851
http://dx.doi.org/10.1016/j.celrep.2021.110020
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author D’Antonio, Matteo
Nguyen, Jennifer P.
Arthur, Timothy D.
Matsui, Hiroko
D’Antonio-Chronowska, Agnieszka
Frazer, Kelly A.
author_facet D’Antonio, Matteo
Nguyen, Jennifer P.
Arthur, Timothy D.
Matsui, Hiroko
D’Antonio-Chronowska, Agnieszka
Frazer, Kelly A.
author_sort D’Antonio, Matteo
collection PubMed
description Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types.
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spelling pubmed-85633432021-11-03 SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues D’Antonio, Matteo Nguyen, Jennifer P. Arthur, Timothy D. Matsui, Hiroko D’Antonio-Chronowska, Agnieszka Frazer, Kelly A. Cell Rep Article Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types. The Author(s). 2021-11-16 2021-11-03 /pmc/articles/PMC8563343/ /pubmed/34762851 http://dx.doi.org/10.1016/j.celrep.2021.110020 Text en © 2021 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
D’Antonio, Matteo
Nguyen, Jennifer P.
Arthur, Timothy D.
Matsui, Hiroko
D’Antonio-Chronowska, Agnieszka
Frazer, Kelly A.
SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues
title SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues
title_full SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues
title_fullStr SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues
title_full_unstemmed SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues
title_short SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues
title_sort sars-cov-2 susceptibility and covid-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563343/
https://www.ncbi.nlm.nih.gov/pubmed/34762851
http://dx.doi.org/10.1016/j.celrep.2021.110020
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