Human genetic variants can influence the severity of symptoms infected with SARS-COV-2.Several genome-wide asso-ciation studies have identified human genomic risk single nucleotide polymorphisms(SNPs)associated with c...Human genetic variants can influence the severity of symptoms infected with SARS-COV-2.Several genome-wide asso-ciation studies have identified human genomic risk single nucleotide polymorphisms(SNPs)associated with coronavirus disease 2019(COVID-19)severity.However,the causal tissues or cell types underlying COVID-19 severity are uncertain.In addition,candidate genes associated with these risk SNPs were investigated based on genomic proximity instead of their functional cellular contexts.Here,we compiled regulatory networks of 77 human contexts and revealed those risk SNPs’enriched cellular contexts and associated risk SNPs with transcription factors,regulatory elements,and target genes.Twenty-one human contexts were identified and grouped into two categories:immune cells and epithelium cells.We further aggregated the regulatory networks of immune cells and epithelium cells.These two aggregated regulatory networks were investigated to reveal their association with risk SNPs’regulation.Two genomic clusters,the chemokine receptors cluster and the oligoadenylate synthetase(OAS)cluster,showed the strongest association with COVID-19 severity,and they had different regulatory programs in immune and epithelium contexts.Our findings were supported by analysis of both SNP array and whole genome sequencing-based genome wide association study(GWAS)summary statistics.展开更多
基金funding from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDPB17)National Key Research and Development Program of China(2020YFA0712402)+2 种基金the National Natural Science Foundation of China(grants 12025107,11871463,61621003,11688101)The Genotype-Tissue Expression(GTEx)Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health,and by NCI,NHGRI,NHLBI,NIDA,NIMH,and NINDSThe data used for the analyses described in this manuscript were obtained from the GTEx Portal under dbGaP accession number phs000424.v8.p2 on 12/09/2020.
文摘Human genetic variants can influence the severity of symptoms infected with SARS-COV-2.Several genome-wide asso-ciation studies have identified human genomic risk single nucleotide polymorphisms(SNPs)associated with coronavirus disease 2019(COVID-19)severity.However,the causal tissues or cell types underlying COVID-19 severity are uncertain.In addition,candidate genes associated with these risk SNPs were investigated based on genomic proximity instead of their functional cellular contexts.Here,we compiled regulatory networks of 77 human contexts and revealed those risk SNPs’enriched cellular contexts and associated risk SNPs with transcription factors,regulatory elements,and target genes.Twenty-one human contexts were identified and grouped into two categories:immune cells and epithelium cells.We further aggregated the regulatory networks of immune cells and epithelium cells.These two aggregated regulatory networks were investigated to reveal their association with risk SNPs’regulation.Two genomic clusters,the chemokine receptors cluster and the oligoadenylate synthetase(OAS)cluster,showed the strongest association with COVID-19 severity,and they had different regulatory programs in immune and epithelium contexts.Our findings were supported by analysis of both SNP array and whole genome sequencing-based genome wide association study(GWAS)summary statistics.
