iScience (Feb 2022)
Optical genome mapping identifies rare structural variations as predisposition factors associated with severe COVID-19
- Nikhil Shri Sahajpal,
- Chi-Yu Jill Lai,
- Alex Hastie,
- Ashis K. Mondal,
- Siavash Raeisi Dehkordi,
- Caspar I. van der Made,
- Olivier Fedrigo,
- Farooq Al-Ajli,
- Sawan Jalnapurkar,
- Marta Byrska-Bishop,
- Rashmi Kanagal-Shamanna,
- Brynn Levy,
- Maximilian Schieck,
- Thomas Illig,
- Silviu-Alin Bacanu,
- Janet S. Chou,
- Adrienne G. Randolph,
- Amyn M. Rojiani,
- Michael C. Zody,
- Catherine A. Brownstein,
- Alan H. Beggs,
- Vineet Bafna,
- Erich D. Jarvis,
- Alexander Hoischen,
- Alka Chaubey,
- Ravindra Kolhe
Affiliations
- Nikhil Shri Sahajpal
- Department of Pathology, Medical College of Georgia, Augusta University, 1120 15th Street, BF-207, Augusta, GA 30912, USA
- Chi-Yu Jill Lai
- Bionano Genomics, Inc., San Diego, CA 92121, USA
- Alex Hastie
- Bionano Genomics, Inc., San Diego, CA 92121, USA
- Ashis K. Mondal
- Department of Pathology, Medical College of Georgia, Augusta University, 1120 15th Street, BF-207, Augusta, GA 30912, USA
- Siavash Raeisi Dehkordi
- Department of Computer Science and Engineering, University of California at San Diego, San Diego, CA 92093, USA
- Caspar I. van der Made
- Department of Human Genetics, Radboud University Medical Center for Infectious Diseases (RCI), Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, and Radboud Expertise Center for Immunodeficiency and Autoinflammation, Radboud University Medical Center, 6525 Nijmegen, the Netherlands
- Olivier Fedrigo
- Vertebrate Genome Lab, The Rockefeller University, New York, NY 10065, USA
- Farooq Al-Ajli
- Vertebrate Genome Lab, The Rockefeller University, New York, NY 10065, USA
- Sawan Jalnapurkar
- Department of Medicine, Medical College of Georgia, Augusta University, GA 30912, USA
- Marta Byrska-Bishop
- New York Genome Center, New York, NY 10013, USA
- Rashmi Kanagal-Shamanna
- Hematopathology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA
- Brynn Levy
- Department of Pathology and Cell Biology, Columbia University Medical Center, New York 10032, USA
- Maximilian Schieck
- Department of Human Genetics, Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover 30625, Germany
- Thomas Illig
- Department of Human Genetics, Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover 30625, Germany; Hannover Unified Biobank (HUB), Hannover 30625, Germany
- Silviu-Alin Bacanu
- Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23284, USA
- Janet S. Chou
- Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA
- Adrienne G. Randolph
- Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children’s Hospital, Boston, MA 02115, USA; Departments of Anesthesia and Pediatrics, Harvard Medical School, Boston, MA 02115, USA
- Amyn M. Rojiani
- Department of Pathology, Medical College of Georgia, Augusta University, 1120 15th Street, BF-207, Augusta, GA 30912, USA
- Michael C. Zody
- New York Genome Center, New York, NY 10013, USA
- Catherine A. Brownstein
- Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- Alan H. Beggs
- Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- Vineet Bafna
- Department of Computer Science and Engineering, University of California at San Diego, San Diego, CA 92093, USA
- Erich D. Jarvis
- Vertebrate Genome Lab, The Rockefeller University, New York, NY 10065, USA; Laboratory of Neurogenetics of Language, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA
- Alexander Hoischen
- Department of Human Genetics, Radboud University Medical Center for Infectious Diseases (RCI), Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, and Radboud Expertise Center for Immunodeficiency and Autoinflammation, Radboud University Medical Center, 6525 Nijmegen, the Netherlands
- Alka Chaubey
- Department of Pathology, Medical College of Georgia, Augusta University, 1120 15th Street, BF-207, Augusta, GA 30912, USA; Bionano Genomics, Inc., San Diego, CA 92121, USA
- Ravindra Kolhe
- Department of Pathology, Medical College of Georgia, Augusta University, 1120 15th Street, BF-207, Augusta, GA 30912, USA; Corresponding author
- Journal volume & issue
-
Vol. 25,
no. 2
p. 103760
Abstract
Summary: Impressive global efforts have identified both rare and common gene variants associated with severe COVID-19 using sequencing technologies. However, these studies lack the sensitivity to accurately detect several classes of variants, especially large structural variants (SVs), which account for a substantial proportion of genetic diversity including clinically relevant variation. We performed optical genome mapping on 52 severely ill COVID-19 patients to identify rare/unique SVs as decisive predisposition factors associated with COVID-19. We identified 7 SVs involving genes implicated in two key host-viral interaction pathways: innate immunity and inflammatory response, and viral replication and spread in nine patients, of which SVs in STK26 and DPP4 genes are the most intriguing candidates. This study is the first to systematically assess the potential role of SVs in the pathogenesis of COVID-19 severity and highlights the need to evaluate SVs along with sequencing variants to comprehensively associate genomic information with interindividual variability in COVID-19 phenotypes.
