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.

Autor: 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., Habegger L; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA., Cantor MN; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA., Rand KA; AncestryDNA, 1300 West Traverse Parkway, Lehi, UT 84043, USA., Hong EL; AncestryDNA, 1300 West Traverse Parkway, Lehi, UT 84043, USA., Reid JG; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA., Ball CA; AncestryDNA, 1300 West Traverse Parkway, Lehi, UT 84043, USA., Baras A; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA., Abecasis GR; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA., Ferreira MA; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Jazyk: angličtina
Zdroj: MedRxiv : the preprint server for health sciences [medRxiv] 2021 Jun 10. Date of Electronic Publication: 2021 Jun 10.
DOI: 10.1101/2020.12.14.20248176
Abstrakt: 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.
Competing Interests: Competing interests J.E.H., J.A.K., A.D., D.S., N.B, A.Y., A.M., R.L., E.M., X.B., D.S., F.S.P.K., J.D.B., C.O’D., A.J.M., D.A.T., A.H.L., J.M., K.W., L.G., S.E.M, H.M.K., L.D., E.S., M.J., S.B., K.S.M, W.J.S., A.R.S., A.E.L., J.M., J.O., L.H., M.N.C., J.G.R., A.B., G.R.A., and M.A.F. are current employees and/or stockholders of Regeneron Genetics Center or Regeneron Pharmaceuticals. G.H.L.R., M.V.C., D.S.P., S.C.K. A.Bal., A.R.G., S.R.M., R.P., M.Z., K.A.R., E.L.H., C.A.B. are current employees at AncestryDNA and may hold equity in AncestryDNA. The other authors declare no competing interests.
Databáze: MEDLINE
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