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Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection.
Dobrindt, Kristina; Hoagland, Daisy A; Seah, Carina; Kassim, Bibi; O'Shea, Callan P; Murphy, Aleta; Iskhakova, Marina; Fernando, Michael B; Powell, Samuel K; Deans, P J Michael; Javidfar, Ben; Peter, Cyril; Møller, Rasmus; Uhl, Skyler A; Garcia, Meilin Fernandez; Kimura, Masaki; Iwasawa, Kentaro; Crary, John F; Kotton, Darrell N; Takebe, Takanori; Huckins, Laura M; tenOever, Benjamin R; Akbarian, Schahram; Brennand, Kristen J.
  • Dobrindt K; Pamela Sklar Division of Psychiatric Genomics, Department of Genetics and Genomics, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Moun
  • Hoagland DA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA; Graduate School of Biomedical Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Seah C; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Kassim B; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • O'Shea CP; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Murphy A; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Iskhakova M; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Fernando MB; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Powell SK; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Deans PJM; Pamela Sklar Division of Psychiatric Genomics, Department of Genetics and Genomics, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Moun
  • Javidfar B; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Peter C; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Møller R; Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA; Graduate School of Biomedical Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Uhl SA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA; Graduate School of Biomedical Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Garcia MF; Pamela Sklar Division of Psychiatric Genomics, Department of Genetics and Genomics, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Moun
  • Kimura M; Division of Gastroenterology, Hepatology and Nutrition, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Center for Stem Cell and Organoid Medicine (CuSTOM), Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
  • Iwasawa K; Division of Gastroenterology, Hepatology and Nutrition, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Center for Stem Cell and Organoid Medicine (CuSTOM), Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
  • Crary JF; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Kotton DN; Center for Regenerative Medicine of Boston University and Boston Medical Center, Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
  • Takebe T; Division of Gastroenterology, Hepatology and Nutrition, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Center for Stem Cell and Organoid Medicine (CuSTOM), Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Institute of Res
  • Huckins LM; Pamela Sklar Division of Psychiatric Genomics, Department of Genetics and Genomics, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Moun
  • tenOever BR; Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA.
  • Akbarian S; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: kristen.brennand@mssm.edu.
  • Brennand KJ; Pamela Sklar Division of Psychiatric Genomics, Department of Genetics and Genomics, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Moun
Stem Cell Reports ; 16(3): 505-518, 2021 03 09.
Article in English | MEDLINE | ID: covidwho-1081358
Preprint
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ABSTRACT
The host response to SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, demonstrates significant interindividual variability. In addition to showing more disease in males, the elderly, and individuals with underlying comorbidities, SARS-CoV-2 can seemingly afflict healthy individuals with profound clinical complications. We hypothesize that, in addition to viral load and host antibody repertoire, host genetic variants influence vulnerability to infection. Here we apply human induced pluripotent stem cell (hiPSC)-based models and CRISPR engineering to explore the host genetics of SARS-CoV-2. We demonstrate that a single-nucleotide polymorphism (rs4702), common in the population and located in the 3' UTR of the protease FURIN, influences alveolar and neuron infection by SARS-CoV-2 in vitro. Thus, we provide a proof-of-principle finding that common genetic variation can have an impact on viral infection and thus contribute to clinical heterogeneity in COVID-19. Ongoing genetic studies will help to identify high-risk individuals, predict clinical complications, and facilitate the discovery of drugs.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Genetic Predisposition to Disease / Polymorphism, Single Nucleotide / COVID-19 Type of study: Etiology study / Experimental Studies / Prognostic study Topics: Variants Limits: Adolescent / Adult / Animals / Female / Humans / Male Language: English Journal: Stem Cell Reports Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Genetic Predisposition to Disease / Polymorphism, Single Nucleotide / COVID-19 Type of study: Etiology study / Experimental Studies / Prognostic study Topics: Variants Limits: Adolescent / Adult / Animals / Female / Humans / Male Language: English Journal: Stem Cell Reports Year: 2021 Document Type: Article