SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a wide variety of tissues
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Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identifyied four genomic loci with suggestive associations for SARS-CoV-2 susceptibility and nineteen for COVID-19 disease severity. Four of these 23 loci likely hadve an ethnicity-specific component. GWAS signals in eleven loci colocalized with eQTLs associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene) including lung, brain, heart, muscle, skin as well as the digestive system and immune system. We performed genetic fine mapping to compute 99% credible SNP sets, which identifyied ten GWAS loci that includedhave 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. Supplementary Tables Table S1: Genome-wide-significant COVID-19 loci Table S2: Colocalization between GWAS signals and eQTLs in 62 tissues at each of the 23 genome-wide significant loci Table S3: Fine mapped loci using eQTL information Table S4: Posterior probabilities of association at each of the 11 fine mapped loci
个体间新型冠状病毒（SARS-CoV-2）易感性与新型冠状病毒肺炎（COVID-19）疾病严重程度的差异，部分源于遗传因素。本研究鉴定出4个与SARS-CoV-2易感性存在提示性关联的基因组位点，以及19个与COVID-19疾病严重程度相关的基因组位点。上述23个位点中，有4个可能存在族群特异性特征。11个位点的全基因组关联研究（Genome-Wide Association Study, GWAS）信号与62种组织/细胞类型中20个基因的表达相关的表达数量性状位点（expression quantitative trait locus, eQTL）发生共定位，单基因对应组织数量范围为1至43种，涉及肺、脑、心脏、肌肉、皮肤以及消化系统与免疫系统。我们开展了遗传精细定位以计算99%可信单核苷酸多态性（single nucleotide polymorphism, SNP）集合，由此鉴定出10个GWAS位点，其可信集合内的SNP数量不超过8个，其中3个位点仅包含1个潜在的因果SNP。本研究表明，个体间观察到的COVID-19多样症状与疾病严重程度，与基因组上影响多种组织类型基因表达水平的变异相关。 补充表格 表S1：全基因组显著COVID-19关联位点 表S2：23个全基因组显著位点所在的62种组织中，GWAS信号与eQTL的共定位结果 表S3：基于eQTL信息的精细定位位点 表S4：11个精细定位位点的关联后验概率
