SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues.
SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues.
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DOI：
10.1016/j.celrep.2021.110020
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发表时间：
2021-11-16
期刊：
影响因子：
8.8
通讯作者：
Frazer KA
中科院分区：
文献类型：
--
作者：
D'Antonio M;Nguyen JP;Arthur TD;Matsui H;COVID-19 Host Genetics Initiative;D'Antonio-Chronowska A;Frazer KA
个体之间SARS-CoV-2易感性和COVID-19疾病严重程度的差异部分是由于遗传因素。在这里，我们确定了4个与SARS-CoV-2易感性相关的基因组位点，19个与COVID-19疾病严重程度相关的基因组位点。这23个基因座中有4个可能有种族特异性成分。在62种组织/细胞类型（范围：1:43组织/基因）中，包括肺、脑、心脏、肌肉、皮肤以及消化系统和免疫系统，11个位点的全基因组关联研究（GWAS）信号与与20个基因表达相关的表达数量性状位点（eQTLs）共定位。我们执行遗传精细作图来计算99%可信SNP集，确定10个GWAS基因座在可信集中具有8个或更少的SNP，其中包括3个基因座具有单个可能的因果SNP。我们的研究表明，在个体之间观察到的COVID-19的不同症状和疾病严重程度与整个基因组的变异有关，影响了各种组织类型中的基因表达水平。D 'Antonio等人表征了69个人体组织中COVID-19疾病的GWAS信号与eqtl之间的关联，以确定因果变异及其潜在的分子机制。他们表明，COVID-19的不同症状和疾病严重程度与影响多种组织中基因表达的变异有关。
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. D’Antonio et al. characterize associations between GWAS signals for COVID-19 disease and eQTLs in 69 human tissues to identify causal variants and their underlying molecular mechanisms. They show that diverse symptoms and disease severity of COVID-19 are associated with variants affecting gene expression in a wide variety of tissues.
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影响因子：
7.7
作者：
Gutierrez-Arcelus M;Lappalainen T;Montgomery SB;Buil A;Ongen H;Yurovsky A;Bryois J;Giger T;Romano L;Planchon A;Falconnet E;Bielser D;Gagnebin M;Padioleau I;Borel C;Letourneau A;Makrythanasis P;Guipponi M;Gehrig C;Antonarakis SE;Dermitzakis ET
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作者：
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DOI：
10.1073/pnas.1815071116
发表时间：
2019-03-12
影响因子：
11.1
作者：
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通讯作者：
Silverman, Robert H.
影响因子：
64.5
作者：
Astle, William J.;Elding, Heather;Soranzo, Nicole
通讯作者：
Soranzo, Nicole
影响因子：
3.5
作者：
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通讯作者：
Hutton, M