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.
Highlights
The SARS-CoV-2 virus has infected more than 220 million individuals worldwide between December 2019 and August 2021, and its associated disease (COVID-19) has reportedly caused >4.5 million deaths (Worldometer, 2021)
Our study shows that SARS-CoV-2 susceptibility and COVID-19 disease severity Genome-wide association study (GWAS) variants are associated with the expression levels of many genes in a wide variety of tissue types
Six severity-associated loci showed heterogeneity in their associations between the European-only and multi-ethnic meta-analyses for one or more phenotypes (Figure 2), suggesting the presence of ethnicity-specific signals, but two were barely below the threshold for association in the European-only meta-analyses (p = 2.6 3 10À7 and p = 2.3 3 10À7, respectively) suggesting that they are underpowered and likely not associated with ethnicity. These analyses show that different intervals in the genome are associated with SARS-CoV-2 susceptibility and COVID-19 disease severity, and the genetic associations within four of these intervals are likely ethnicity specific
Summary
The SARS-CoV-2 virus has infected more than 220 million individuals worldwide between December 2019 and August 2021, and its associated disease (COVID-19) has reportedly caused >4.5 million deaths (Worldometer, 2021). Several risk factors associated with SARS-CoV-2 infection and COVID-19 disease severity have been identified, including older age; sex; ethnicity; blood type; and cardiovascular, respiratory, and kidney diseases (Atkins et al, 2020; Cummings et al, 2020; Guan et al, 2020; Horowitz et al, 2021; Mackey et al, 2021; Richardson et al, 2020; Zhou et al, 2020).
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