Whole-genome sequencing reveals host factors underlying critical COVID-19

After infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and…

• UO
  University of Pennsylvania

  Awards: UL1TR001878, phs000424
• UO
  University of Washington
• JH
  Johns Hopkins University

  Awards: RC2 AG036495, RC4 AG039029, COVID-19
• WT
  Wellcome Trust

  Awards: 204979/Z/16/Z, 204979, 223164, 223164/Z/21/Z
• L
  LifeArc
• UR
  UK Research and Innovation

  Awards: MC_PC_1905, MC_PC_19025, MC_PC_20029, MRNO2995X/1
• GC
  Georgia Clinical and Translational Science Alliance
• UO
  University of Pennsylvania Health System
• CR
  Cancer Research UK
• NI
  National Institute for Health and Care Research
• DO
  Department of Health and Social Care
• IC
  Intensive Care Society
• PH
  Public Health England
• DF
  Department for International Development
• NI
  National Institutes of Health

  Awards: RC2 AG036495, U01AG009740, UL1TR001878, NIA U01AG009740, phs000424.v8.p2, COVID-19, RC4 AG039029
• PS
  Perelman School of Medicine, University of Pennsylvania

  Award: UL1TR001878
• MR
  Medical Research Council

  Awards: MC_EX_MR/M009203/1, MC_UU_00007/15, MR/N02995X/1, MR/R026408/1, MC_PC_17228, MC_PC_14089, MC_PC_20029, MC_PC_19025, MR/P00167X/1, MC_UU_00007/10, COVID-19, MRNO2995X/1
• BA
  Biotechnology and Biological Sciences Research Council

  Awards: BBS/E/D/20002172, /30002275, BBS/E/D/30002277, BBS/E/D/30002275, BBS/E/D/10002070
• NI
  National Institute on Aging

  Awards: RC2 AG036495, RC4 AG039029, NIA U01AG009740, U01AG009740
• NH
  National Heart, Lung, and Blood Institute

  Award: UL1TR001878
• NI
  National Institute of Mental Health
• NI
  National Institute on Drug Abuse
• NH
  National Human Genome Research Institute
• NO
  NIH Office of the Director
• NC
  National Cancer Institute

  Award: UL1TR001878
• NI
  National Institute of Neurological Disorders and Stroke

  Award: phs000424.v8.p2
• NC
  National Center for Advancing Translational Sciences

  Award: UL1TR001878
• CF
  Common Fund