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,
Agnieszka D’Antonio-Chronowska,
Kelly A. Frazer
Affiliations
Matteo D’Antonio
Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA; Corresponding author
Jennifer P. Nguyen
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
Timothy D. Arthur
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
Hiroko Matsui
Institute of Genomic Medicine, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA
Agnieszka D’Antonio-Chronowska
Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA
Kelly A. Frazer
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; Corresponding author
Summary: 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.
