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

Matteo D'Antonio; Jennifer P Nguyen; Timothy D Arthur; Hiroko Matsui; COVID-19 Host Genetics Initiative; Agnieszka D'Antonio-Chronowska; Kelly A Frazer

doi:10.1016/j.celrep.2021.110020

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

Cell Rep. 2021 Nov 16;37(7):110020. doi: 10.1016/j.celrep.2021.110020. Epub 2021 Nov 3.

Authors

Matteo D'Antonio¹, Jennifer P Nguyen², Timothy D Arthur³, Hiroko Matsui⁴; COVID-19 Host Genetics Initiative; Agnieszka D'Antonio-Chronowska⁵, Kelly A Frazer⁶

Affiliations

¹ Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: madantonio@health.ucsd.edu.
² 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.
³ 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.
⁴ Institute of Genomic Medicine, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA.
⁵ Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
⁶ 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.

Abstract

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.

Keywords: COVID-19; GWAS; SARS-CoV-2; colocalization; eQTL.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

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

Abstract

Publication types

MeSH terms

Grants and funding