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

被引：33

作者：

D'Antonio, Matteo ^{[1
]}

Nguyen, Jennifer P. ^{[2
,3
]}

Arthur, Timothy D. ^{[2
,4
]}

Matsui, Hiroko

D'Antonio-Chronowska, Agnieszka ^{[1
]}

Frazer, Kelly A. ^{[1
,5
]}

机构：

[1] Univ Calif San Diego, Dept Pediat, San Diego, CA 92093 USA

[2] Univ Calif San Diego, Dept Biomed Informat, San Diego, CA 92093 USA

[3] Univ Calif San Diego, Bioinformat & Syst Biol Grad Program, San Diego, CA 92093 USA

[4] Univ Calif San Diego, Biomed Sci Grad Program, San Diego, CA 92093 USA

[5] Univ Calif San Diego, Inst Genom Med, 9500 Gilman Dr, La Jolla, CA 92093 USA

来源：

CELL REPORTS | 2021年 / 37卷 / 07期

关键词：

GENOME-WIDE ASSOCIATION; NEW-YORK-CITY; TAU GENE; CORONAVIRUS; INFECTION; INVERSION; HAPLOTYPE; OUTCOMES; INNATE; CELLS;

D O I：

10.1016/j.celrep.2021.110020

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

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