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.
【초록키워드】 COVID-19, coronavirus disease, severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, Coronavirus disease 2019, ACE2, coronavirus, SARS-COV-2 infection, disease severity, Genetic, allele frequency, variant, risk, outcome, severe acute respiratory syndrome Coronavirus, virus, angiotensin-converting enzyme 2, variants, Genome-wide association study, minor allele frequency, ACE2 expression, MHC, association, Angiotensin-converting enzyme, Evidence, IFNAR2, angiotensin, Odds ratio, severe disease, acute respiratory syndrome, DPP9, acute respiratory syndrome coronavirus, enzyme, individual, common variants, human host cells, LZTFL1, IMPROVE, identify, reported, replicate, cause, reduce, downregulate, clinical factor, human host cell, 【제목키워드】 COVID-19, ACE2, Genetic, risk, Evidence, Analysis, risk score, provide, influence,