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; COVID-19 Host Genetics Initiative; D'Antonio-Chronowska, Agnieszka; Frazer, Kelly A

doi:10.1016/j.celrep.2021.110020

Article (Scientific journals)

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 et al.

2021 • In Cell Reports, 37 (7), p. 110020

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https://hdl.handle.net/2268/308412

DOI
10.1016/j.celrep.2021.110020

PubMed
34762851

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Keywords :

COVID-19; GWAS; SARS-CoV-2; colocalization; eQTL; COVID-19/genetics; Chromosome Mapping/methods; Computational Biology/methods; Databases, Genetic; Ethnicity/genetics; Gene Expression/genetics; Gene Expression Profiling/methods; Genetic Predisposition to Disease/genetics; Genetic Variation/genetics; Genome-Wide Association Study/methods; Humans; Organ Specificity/genetics; Polymorphism, Single Nucleotide/genetics; Quantitative Trait Loci/genetics; SARS-CoV-2/genetics; SARS-CoV-2/pathogenicity; Severity of Illness Index; Transcriptome/genetics; Chromosome Mapping; Computational Biology; Ethnic Groups; Gene Expression; Gene Expression Profiling; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Organ Specificity; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Transcriptome; Biochemistry, Genetics and Molecular Biology (all); General Biochemistry, Genetics and Molecular Biology

Abstract :

[en] 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.

Disciplines :

Immunology & infectious disease

Author, co-author :

D'Antonio, Matteo; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: madantonio@health.ucsd.edu

Nguyen, Jennifer P; Department of Biomedical Informatics, University of California, San Diego, La Jolla, CA 92093, USA, Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA

Arthur, Timothy D; Department of Biomedical Informatics, University of California, San Diego, La Jolla, CA 92093, USA, Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA

Matsui, Hiroko; Institute of Genomic Medicine, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA

COVID-19 Host Genetics Initiative

D'Antonio-Chronowska, Agnieszka; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA

Frazer, Kelly A; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA, Institute of Genomic Medicine, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA. Electronic address: kafrazer@health.ucsd.edu

Other collaborator :

Moutschen, Michel ; Centre Hospitalier Universitaire de Liège - CHU > > Service des maladies infectieuses - médecine interne

Language :

English

Title :

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

Publication date :

2021

Journal title :

Cell Reports

eISSN :

2211-1247

Publisher :

Elsevier B.V., United States

Volume :

Issue :

Pages :

110020

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://api.elsevier.com/content/article/PII:S2211124721015023?httpAccept=text/xml

Funders :

NIH - National Institutes of Health
NHGRI - National Human Genome Research Institute
UCSD - University of California, San Diego

Funding text :

This work was supported by Emergency COVID-19 Seed Award from the Tobacco-Related Disease Research Program of the University of California , grant R00RG2716 , and by the NHGRI CEGS grant RM1HG011558 . J.P.N. and T.D.A. were supported by an NIH training grant ( T15LM011271 ).

Commentary :

A complete list of the members of the COVID-19 Host Genetics Initiative and their affiliations is provided at https://docs.google.com/spreadsheets/d/1cp9pFeFUxXz5WMjRFv4X-AM1Hlc0iXYJa1rorSSj2Dc.

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