{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Horowitz JE"],"funding":["NCATS NIH HHS"],"pagination":["382-392"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9005345"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["54(4)"],"pubmed_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<sup>-</sup><sup>8</sup>) and reduces the risk of SARS-CoV-2 infection by 40% (odds ratio = 0.60, P = 4.5 × 10<sup>-</sup><sup>13</sup>), 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 t"],"journal":["Nature genetics"],"pubmed_title":["Genome-wide analysis provides genetic evidence that ACE2 influences COVID-19 risk and yields risk scores associated with severe disease."],"pmcid":["PMC9005345"],"funding_grant_id":["UL1 TR001878"],"pubmed_authors":["Siminovitch K","Tzoneva G","Guvenek A","Roberts GHL","Persaud T","Wolf SE","Zhang M","Verweij N","Marchini J","O'Keeffe S","Maxwell E","Baltzell A","Baras A","Haas M","Watanabe K","LeBlanc MG","Widom L","Zhang B","Akbari P","Riaz M","Kang HM","Locke AE","Ayer A","Kosmicki JA","Freudenberg J","Justice AE","Ritchie MD","Backman JD","Stahl E","Gelfman S","Nakka P","Lin N","Kessler M","Leader JB","Hindy G","Carey DJ","Eom G","Horowitz JE","Knight SC","Kim M","Mighty J","Sirugo G","Polanco T","Deubler A","Salerno W","Lotta LA","Li A","Nishtala N","Jones MB","McCarthy SE","Lopez A","Maxwell EK","Ghosh A","Manoochehri K","Boutkov B","Cantor M","Forsythe C","Balasubramanian S","Kapoor M","Ye B","Donato V","Fernandez D","Fuller ED","Coignet MV","Yadav A","Bai X","Xin J","Regeneron Genetics Center","Mirshahi T","Damask A","Locke A","Bovijn J","Marcketta A","Economides A","Panea R","Guturu H","Staples JC","Paulding C","Rajagopal V","Nunez S","Rana N","Abecasis GR","Mansfield AJ","Coppola G","Jorgenson E","Averitt A","Rand KA","Verma A","Park DS","McCurdy SR","Sharma D","Lanche R","Sun D","Nafde M","Krasheninina O","Howell K","Chen S","Backman J","Sun K","Abecasis G","Lattari M","Turissini DA","Li D","Kury FSP","Habegger L","Shuldiner AR","Pradhan M","Chen E","Jones M","Orelus M","Martinez H","Karalis K","Padilla MS","De T","Ulloa RH","Ziyatdinov A","Malhotra S","Rader DJ","Gillies C","Chim SM","Rasool A","Moscati A","Gatta GD","Partha R","Overton JD","Mitra G","Hawes A","Hong EL","Dobbyn L","Shuldiner A","Cantor MN","Gokhale S","Khrimian L","Schleicher TD","Li AH","Mbatchou J","O'Dushlaine C","Mitnaul LJ","Salerno WJ","Banerjee N","Khalid S","Pavlopoulos E","Reid JG","Staples J","Gurski L","Girshick AR","Di Gioia A","Beechert C","Gu Z","Rodriguez-Flores J","Bao S","Sidore C","Sosina O","Ball CA","Liu D","Praveen K","Miloscio L","Ferreira MAR"],"additional_accession":[]},"is_claimable":false,"name":"Genome-wide analysis provides genetic evidence that ACE2 influences COVID-19 risk and yields risk scores associated with severe disease.","description":"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<sup>-</sup><sup>8</sup>) and reduces the risk of SARS-CoV-2 infection by 40% (odds ratio = 0.60, P = 4.5 × 10<sup>-</sup><sup>13</sup>), 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 t","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2026-05-10T01:34:47.884Z","creation":"2024-11-09T04:35:30.248Z"},"accession":"S-EPMC9005345","cross_references":{"pubmed":["35241825"],"doi":["10.1038/s41588-021-01006-7"]}}