Genome-wide analysis in 756,646 individuals provides first genetic evidence that <i>ACE2</i> expression influences COVID-19 risk and yields genetic risk scores predictive of severe disease.

Horowitz, J E; Kosmicki, J A; Damask, A; Sharma, D; Roberts, G H L; Justice, A E; Banerjee, N; Coignet, M V; Yadav, A; Leader, J B; Marcketta, A; Park, D S; Lanche, R; Maxwell, E; Knight, S C; Bai, X; Guturu, H; Sun, D; Baltzell, A; Kury, F S P; Backman, J D; Girshick, A R; O'Dushlaine, C; McCurdy, S R; Partha, R; Mansfield, A J; Turissini, D A; Li, A H; Zhang, M; Mbatchou, J; Watanabe, K; Gurski, L; McCarthy, S E; Kang, H M; Dobbyn, L; Stahl, E; Verma, A; Sirugo, G; Ritchie, M D; Jones, M; Balasubramanian, S; Siminovitch, K; Salerno, W J; Shuldiner, A R; Rader, D J; Mirshahi, T; Locke, A E; Marchini, J; Overton, J D; Carey, D J

Genome-wide analysis in 756,646 individuals provides first genetic evidence that ACE2 expression influences COVID-19 risk and yields genetic risk scores predictive of severe disease.

Horowitz, J E; Kosmicki, J A; Damask, A; Sharma, D; Roberts, G H L; Justice, A E; Banerjee, N; Coignet, M V; Yadav, A; Leader, J B; Marcketta, A; Park, D S; Lanche, R; Maxwell, E; Knight, S C; Bai, X; Guturu, H; Sun, D; Baltzell, A; Kury, F S P; Backman, J D; Girshick, A R; O'Dushlaine, C; McCurdy, S R; Partha, R; Mansfield, A J; Turissini, D A; Li, A H; Zhang, M; Mbatchou, J; Watanabe, K; Gurski, L; McCarthy, S E; Kang, H M; Dobbyn, L; Stahl, E; Verma, A; Sirugo, G; Ritchie, M D; Jones, M; Balasubramanian, S; Siminovitch, K; Salerno, W J; Shuldiner, A R; Rader, D J; Mirshahi, T; Locke, A E; Marchini, J; Overton, J D; Carey, D J.

Afiliación

Horowitz JE; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Kosmicki JA; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Damask A; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Sharma D; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Roberts GHL; AncestryDNA, 1300 West Traverse Parkway, Lehi, UT 84043, USA.
Justice AE; Geisinger, Danville, PA, 17822, USA.
Banerjee N; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Coignet MV; AncestryDNA, 1300 West Traverse Parkway, Lehi, UT 84043, USA.
Yadav A; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Leader JB; Geisinger, Danville, PA, 17822, USA.
Marcketta A; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Park DS; AncestryDNA, 1300 West Traverse Parkway, Lehi, UT 84043, USA.
Lanche R; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Maxwell E; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Knight SC; AncestryDNA, 1300 West Traverse Parkway, Lehi, UT 84043, USA.
Bai X; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Guturu H; AncestryDNA, 1300 West Traverse Parkway, Lehi, UT 84043, USA.
Sun D; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Baltzell A; AncestryDNA, 1300 West Traverse Parkway, Lehi, UT 84043, USA.
Kury FSP; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Backman JD; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Girshick AR; AncestryDNA, 1300 West Traverse Parkway, Lehi, UT 84043, USA.
O'Dushlaine C; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
McCurdy SR; AncestryDNA, 1300 West Traverse Parkway, Lehi, UT 84043, USA.
Partha R; AncestryDNA, 1300 West Traverse Parkway, Lehi, UT 84043, USA.
Mansfield AJ; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Turissini DA; AncestryDNA, 1300 West Traverse Parkway, Lehi, UT 84043, USA.
Li AH; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Zhang M; AncestryDNA, 1300 West Traverse Parkway, Lehi, UT 84043, USA.
Mbatchou J; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Watanabe K; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Gurski L; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
McCarthy SE; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Kang HM; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Dobbyn L; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Stahl E; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Verma A; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Sirugo G; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Ritchie MD; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Jones M; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Balasubramanian S; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Siminovitch K; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Salerno WJ; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Shuldiner AR; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Rader DJ; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Mirshahi T; Geisinger, Danville, PA, 17822, USA.
Locke AE; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Marchini J; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Overton JD; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Carey DJ; Geisinger, Danville, PA, 17822, USA.

medRxiv ; 2021 Jun 10.

Article en En | MEDLINE | ID: mdl-33619501

ABSTRACT

ABSTRACT

SARS-CoV-2 enters host cells by binding angiotensin-converting enzyme 2 (ACE2). Through a genome-wide association study, we show that a rare variant (MAF = 0.3%, odds ratio 0.60, P=4.5×10-13) that down-regulates ACE2 expression reduces risk of COVID-19 disease, providing human genetics support for the hypothesis that ACE2 levels influence COVID-19 risk. Further, we show that common genetic variants define a risk score that predicts severe disease among COVID-19 cases.

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Aspecto: Patient_preference Idioma: En Revista: MedRxiv Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos

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