Genome-wide analysis provides genetic evidence that ACE2 influences COVID-19 risk and yields risk scores associated with severe disease.
Nat Genet
; 54(4): 382-392, 2022 04.
Article
em En
| MEDLINE
| ID: mdl-35241825
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-19 risk. We also replicate the associations of six previously reported risk variants, of which four were further associated with worse outcomes in individuals infected with the virus (in/near LZTFL1, MHC, DPP9 and IFNAR2). Lastly, we show that common variants define a risk score that is strongly associated with severe disease among cases and modestly improves the prediction of disease severity relative to demographic and clinical factors alone.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
4_TD
Base de dados:
MEDLINE
Assunto principal:
COVID-19
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Aspecto:
Patient_preference
Limite:
Humans
Idioma:
En
Revista:
Nat Genet
Ano de publicação:
2022
Tipo de documento:
Article