Pulse Brain · Growing Health Evidence Index
Peer-reviewed

Genetic mechanisms of critical illness in COVID-19

The GenOMICC Investigators, Erola Pairo‐Castineira, The ISARIC4C Investigators, The COVID-19 Human Genetics Initiative, 23andMe Investigators, BRACOVID Investigators, Gen-COVID Investigators, Sara Clohisey, Lucija Klarić, Andrew D. Bretherick, Konrad Rawlik, Dorota Pasko, Susan Walker, Nick Parkinson, Max Head Fourman, Clark D Russell, James Furniss, Anne Richmond, Viktoria‐Eleni Gountouna, Nicola Wrobel, David A Harrison, Bo Wang, Yang Wu, Alison Meynert, Fiona Griffiths, Wilna Oosthuyzen, Athanasios Kousathanas, Loukas Moutsianas, Zhijian Yang, Ranran Zhai, Chenqing Zheng, Graeme R. Grimes, Rupert Beale, Jonathan Millar, Barbara Shih, Seán Keating, Marie Zechner, Chris Haley, David J. Porteous, Caroline Hayward, Jian Yang, Julian C. Knight, Charlotte Summers, Manu Shankar‐Hari, Paul Klenerman, Lance Turtle, Antonia Ho, Shona C. Moore, Charles Hinds, Peter Horby, Alistair Nichol, David M. Maslove, Lowell Ling, Danny McAuley, Hugh Montgomery, Timothy Walsh, Alexandre C. Pereira, Alessandra Renieri, Xia Shen, Chris P. Ponting, Angie Fawkes, Albert Tenesa, Mark J. Caulfield, Richard H. Scott, Kathy Rowan, Lee Murphy, Peter Openshaw, Malcolm G. Semple, Andrew Law, Véronique Vitart, James F. Wilson, J. Kenneth Baillie

Nature · 2020

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Summary

) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice.

Source type
Peer-reviewed study
DOI
10.1038/s41586-020-03065-y
Catalogue ID
BFmokjo2bz-zrglta
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