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A catalog of associations between rare coding variants and COVID-19 outcomes.
Kosmicki, J A; Horowitz, J E; Banerjee, N; Lanche, R; Marcketta, A; Maxwell, E; Bai, X; Sun, D; Backman, J D; Sharma, D; Kang, H M; O'Dushlaine, C; Yadav, A; Mansfield, A J; Li, A H; Watanabe, K; Gurski, L; McCarthy, S E; Locke, A E; Khalid, S; O'Keeffe, S; Mbatchou, J; Chazara, O; Huang, Y; Kvikstad, E; O'Neill, A; Nioi, P; Parker, M M; Petrovski, S; Runz, H; Szustakowski, J D; Wang, Q; Wong, E; Cordova-Palomera, A; Smith, E N; Szalma, S; Zheng, X; Esmaeeli, S; Davis, J W; Lai, Y-P; Chen, X; Justice, A E; Leader, J B; Mirshahi, T; Carey, D J; Verma, A; Sirugo, G; Ritchie, M D; Rader, D J; Povysil, G.
Affiliation
  • Kosmicki JA; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
  • Horowitz JE; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
  • Banerjee N; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
  • Lanche R; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
  • Marcketta A; 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.
  • Bai X; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
  • Sun D; 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.
  • Sharma D; 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.
  • O'Dushlaine C; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
  • Yadav A; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
  • Mansfield AJ; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
  • Li AH; 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.
  • Locke AE; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
  • Khalid S; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
  • O'Keeffe S; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
  • Mbatchou J; Regeneron Genetics Center, 777 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
  • Chazara O; Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.
  • Huang Y; Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.
  • Kvikstad E; Bristol Myers Squibb, Route 206 and Province Line Road, Princeton, NJ 08543, USA.
  • O'Neill A; Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.
  • Nioi P; Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.
  • Parker MM; Alnylam Pharmaceuticals, 675 West Kendall St, Cambridge, MA 02142, USA.
  • Petrovski S; Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.
  • Runz H; Biogen, 300 Binney St, Cambridge, MA 02142, USA.
  • Szustakowski JD; Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.
  • Wang Q; Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.
  • Wong E; Biogen, 300 Binney St, Cambridge, MA 02142, USA.
  • Cordova-Palomera A; Takeda California Inc., 9625 Towne Centre Dr, San Diego, CA 92121, USA.
  • Smith EN; Takeda California Inc., 9625 Towne Centre Dr, San Diego, CA 92121, USA.
  • Szalma S; Takeda California Inc., 9625 Towne Centre Dr, San Diego, CA 92121, USA.
  • Zheng X; AbbVie, Inc., 1 N. Waukegan Rd, North Chicago, IL 60064, USA.
  • Esmaeeli S; AbbVie, Inc., 1 N. Waukegan Rd, North Chicago, IL 60064, USA.
  • Davis JW; AbbVie, Inc., 1 N. Waukegan Rd, North Chicago, IL 60064, USA.
  • Lai YP; Pfizer, Inc., 1 Portland Street, Cambridge MA 02139, USA.
  • Chen X; Pfizer, Inc., 1 Portland Street, Cambridge MA 02139, USA.
  • Justice AE; Geisinger, Danville, PA, 17822, USA.
  • Leader JB; Geisinger, Danville, PA, 17822, USA.
  • Mirshahi T; Geisinger, Danville, PA, 17822, USA.
  • Carey DJ; Geisinger, Danville, PA, 17822, 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.
  • Rader DJ; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Povysil G; Institute for Genomic Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
medRxiv ; 2021 Feb 27.
Article in En | MEDLINE | ID: mdl-33655273
ABSTRACT
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease-19 (COVID-19), a respiratory illness that can result in hospitalization or death. We investigated associations between rare genetic variants and seven COVID-19 outcomes in 543,213 individuals, including 8,248 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome-wide or when specifically focusing on (i) 14 interferon pathway genes in which rare deleterious variants have been reported in severe COVID-19 patients; (ii) 167 genes located in COVID-19 GWAS risk loci; or (iii) 32 additional genes of immunologic relevance and/or therapeutic potential. Our analyses indicate there are no significant associations with rare protein-coding variants with detectable effect sizes at our current sample sizes. Analyses will be updated as additional data become available, with results publicly browsable at https//rgc-covid19.regeneron.com.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Risk_factors_studies Language: En Journal: MedRxiv Year: 2021 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Risk_factors_studies Language: En Journal: MedRxiv Year: 2021 Document type: Article Affiliation country: