2022
DOI: 10.1038/s41588-021-01006-7
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Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters human host cells via angiotensin-converting enzyme 2 (ACE2) and causes coronavirus disease 2019 (COVID-19). Here, through a genome-wide association study, we identify a variant (rs190509934, minor allele frequency 0.2–2%) that downregulates ACE2 expression by 37% (P = 2.7 × 10−8) and reduces the risk of SARS-CoV-2 infection by 40% (odds ratio = 0.60, P = 4.5 × 10−13), providing human genetic evidence that ACE2 expression levels influence COVID… Show more

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Cited by 102 publications
(74 citation statements)
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“…In this study, the GWAS study showed two plausible genome-wide significant associations on chromosomes 5q32 and 11p12 in EUR ancestral group in our overall susceptibility model by The first reported genome-wide association signals were at loci 3p21.31 and 9q34.2, which revealed the association of protein-coding genes that regulate viral attachment and host immune response (LC6A20, LZTFL1, CCR9, FYCO1, CXCR6, and XCR1) and ABO blood group to severe COVID-19 disease, respectively [33]. These associations were replicated in subsequent studies [10,34,35]. Results of a genetic study of 2244 critically ill patients with COVID-19 in intensive care units across the UK identified associations on chromosomes 12q24.…”
Section: Discussionsupporting
confidence: 53%
See 1 more Smart Citation
“…In this study, the GWAS study showed two plausible genome-wide significant associations on chromosomes 5q32 and 11p12 in EUR ancestral group in our overall susceptibility model by The first reported genome-wide association signals were at loci 3p21.31 and 9q34.2, which revealed the association of protein-coding genes that regulate viral attachment and host immune response (LC6A20, LZTFL1, CCR9, FYCO1, CXCR6, and XCR1) and ABO blood group to severe COVID-19 disease, respectively [33]. These associations were replicated in subsequent studies [10,34,35]. Results of a genetic study of 2244 critically ill patients with COVID-19 in intensive care units across the UK identified associations on chromosomes 12q24.…”
Section: Discussionsupporting
confidence: 53%
“…The first reported genome-wide association signals were at loci 3p21.31 and 9q34.2, which revealed the association of protein-coding genes that regulate viral attachment and host immune response (LC6A20, LZTFL1, CCR9, FYCO1, CXCR6, and XCR1) and ABO blood group to severe COVID-19 disease, respectively[33]. These associations were replicated in subsequent studies[10,34,35]. Results of a genetic study of 2244 critically ill patients with COVID-19 in intensive care units across the UK identified associations on chromosomes 12q24.13, 19p13.2, 19p13.3, and 21q22.1, revealed the genes with innate immunity (IFNAR2 and OAS) and host-driven lung inflammatory injury (DPP9, TYK2, and CCR2)[8].…”
Section: Discussionmentioning
confidence: 96%
“…A second infection susceptibility locus is ACE2 , which is worth mentioning because the gene encodes a key protein involved in the viral entry pathway of SARS viruses 2 4 . GWAS by Horowitz et al 56 and COVID-19 HGI 51 point to a protective variant (rs190509934) 60 bp upstream of the ACE2 gene. This variant, which is rare among individuals of European ancestry (0.2% in the Genome Aggregation Database (gnomAD)), but more common in South Asians (2.7%) was associated with a 39% reduction in ACE2 expression in liver tissues.…”
Section: Genetic Findingsmentioning
confidence: 99%
“…These variants could also contribute to vaccine responsiveness. For instance, a large-scale GWAS study has reported that a rare variant in the ACE2 gene down-regulated ACE2 expression, and hence, reduces the risk of COVID-19 ( 115 ). Such variants could also modulate the response to vaccines that are based on live attenuated virus, if they depend on the interaction between ACE2 and SARS-CoV-2 spike protein.…”
Section: Immunogenomics and Vaccinomics Of Sars-cov-2mentioning
confidence: 99%