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

Authors: Athanasios Kousathanas, Erola Pairo‐Castineira, Konrad Rawlik, A. Stuckey, Christopher A. Odhams, Susan Walker, Clark D Russell, Tomas Malinauskas, Yang Wu, Jonathan Millar, Xia Shen, Katherine S. Elliott, Fiona Griffiths, Wilna Oosthuyzen, Kirstie Morrice, Seán Keating, Bo Wang, Daniel R. Rhodes, Lucija Klarić, Marie Zechner, Nick Parkinson, Afshan Siddiq, Peter Goddard, Sally Donovan, David M. Maslove, Alistair Nichol, Malcolm G. Semple, Tala Zainy, F. Maleady-Crowe, Linda Todd, Shahla Salehi, Julian C. Knight, Greg Elgar, G. C. Chan, Prabhu Arumugam, Christine Patch, Augusto Rendon, David Bentley, Clare Kingsley, Jack A. Kosmicki, Julie Horowitz, Aris Baras, Gonçalo R. Abecasis, Manuel A. R. Ferreira, Anne E. Justice, Tooraj Mirshahi, Matthew T. Oetjens, Daniel J. Rader, Marylyn D. Ritchie, Anurag Verma, Tom Fowler, Manu Shankar‐Hari, Charlotte Summers, Charles Hinds, Peter Horby, Lowell Ling, Daniel F. McAuley, Hugh Montgomery, Peter Openshaw, Paul Elliott, Timothy Walsh, Albert Tenesa, GenOMICC investigators, GenOMICC co-investigators, J. Kenneth Baillie, Colin B. Begg, Sara Clohisey, Charles Hinds, Peter Horby, Julian Knight, Lowell Ling, David M. Maslove, Danny McAuley, Johnny Millar, Hugh Montgomery, Alistair Nichol, Peter J. M. Openshaw, Alexandre C. Pereira, Chris P. Ponting, Kathy Rowan, Malcolm G. Semple, Manu Shankar‐Hari, Charlotte Summers, Timothy Walsh, Latha Aravindan, Ruth Armstrong, Heather Biggs, Ceilia Boz, Adam Brown, Richard Clark, Audrey Coutts, J. Terrence Coyle, Louise Cullum, Sukamal Das, Nicky Day, Lorna Donnelly, Esther Duncan, Angie Fawkes, Paul Finernan, Max Head Fourman, Anita Furlong, James Furniss, Bernadette Gallagher, Tammy Gilchrist, Ailsa Golightly, Fiona Griffiths, Katarzyna Hafezi, Debbie Hamilton, Ross Hendry, Andy Law, Dawn Law, R. M. Law, Sarah Law, Rebecca Lidstone-Scott, Louise MacGillivray, Alan Maclean, Hanning Mal, Sarah McCafferty, Ellie Mcmaster, Jen Meikle, Shona C. Moore, Kirstie Morrice, Lee Murphy, Sheena Murphy, Mybaya Hellen, Wilna Oosthuyzen, Chenqing Zheng, Jiantao Chen, Nick Parkinson, Trevor Paterson, Katherine Schon, Andrew Stenhouse, Mihaela Das, Maaike Swets, Helen Szoor-McElhinney, Filip Taneski, Lance Turtle, Tony Wackett, Mairi Ward, Jane Weaver, Nicola Wrobel, Marie Zechner, Gill Arbane, Aneta Bociek, Sara Campos, Neus Grau, Tim Jones, Rosario Lim, Martina Marotti, Marlies Ostermann, Manu Shankar‐Hari, R. Chris Whitton, Barts Health NHS Trust team, Zoe Alldis, Raine Astin-Chamberlain, Fatima Bibi, Jack Biddle, Sarah Blow, Matthew L. Bolton, Catherine Borra, Ruth Bowles, Maudrian Burton, Yasmin Choudhury, David Collier, Amber Cox, Amy Easthope, Patrizia Ebano, Stavros Fotiadis, Jana Gurasashvili, Rosslyn Halls, Pippa Hartridge, Delordson Kallon, Jamila Kassam, Ivone Lancoma-Malcolm, Maninderpal Matharu, P. May, Oliver Mitchelmore, Tabitha Newman, Mital Patel, Jane Pheby, Irene Pinzuti, Zoe Prime, Oleksandra Prysyazhna, Julian Shiel, Melanie Taylor, Carey Tierney, S. M. Wood, Anne Zak, Olivier Zongo, Stephen Bonner, Keith Hugill, Jessica Jones, Steven Liggett, Evie Headlam, Nageswar Bandla, Minnie Gellamucho, Michelle Davies, C. C. Thompson, Marwa Abdelrazik, Dhanalakshmi Bakthavatsalam, Munzir Elhassan, Arunkumar Ganesan, Anne Haldeos, Jerónimo Moreno-Cuesta, Dharam Purohit, Rachel Vincent, Kugan Xavier, Rohit Kumar, Alasdair Frater, Malik Saleem, David Carter, Samuel Jenkins, Zoe Lamond, Alanna Wall, Jaime Fernandez-Roman, David Hamilton, Emily Johnson, Brian Johnston, Maria Lopez Martinez, Suleman Mulla, David Shaw, Alicia Waite, Victoria Waugh, Ingeborg Welters, Karen Williams, Anna Cavazza, Maeve Cockrell, Eleanor Corcoran, Maria Depante, Clare Finney, Ellen Jerome, Mark McPhail, Monalisa Nayak, Harriet Noble, Kevin O’Reilly, Evita Pappa, Rohit Saha, Sian Saha, John Smith, Abigail Knighton, David Antcliffe, Dorota Banach, Stephen J. Brett, Phoebe Coghlan, Ziortza Fernandez, Anthony Gordon, Roceld Rojo, Sonia Sousa Arias, Maie Templeton, Megan Meredith, Lucy Morris, Lucy Ryan, Amy Clark, Julia Sampson, Cecilia Peters, Martin Dent, Margaret Langley, Saima Ashraf, Shuying Wei, Angela Andrew, Archana Bashyal, Neil Davidson, Paula Hutton, Stuart McKechnie, Jean Wilson, David Baptista, Rebecca Crowe, Rita Fernandes, Rosaleen Herdman-Grant, Anna Joseph, Denise O’Connor, Meryem Allen, Adam Loveridge, India McKenley, Eriko Morino, Andrés Naranjo, Richard Simms, Kathryn Sollesta, Andrew Swain, Harish Venkatesh, Jacyntha Khera, Jonathan Fox, Royal Infirmary of Edinburgh team, Gillian Andrew, J. Kenneth Baillie, Lucy Barclay, Marie Callaghan, Rachael Campbell, Sarah J. Clark, Dave Hope, Lucy Marshall, Corrienne McCulloch, Kate Briton, Jo Singleton, Sophie Birch, Lutece Brimfield, Zoe Daly, David Pogson, Steve Rose, Angela Nown, Ceri Battle, Elaine Brinkworth, Rachel Harford, Carl Murphy, Luke Newey, Tabitha Rees, Marie Williams, Sophie Arnold, Petra Polgarova, Katerina Stroud, Charlotte Summers, Eoghan Meaney, Megan Jones, Anthony Ng, Shruti Agrawal, Nazima Pathan, Deborah White, Esther Daubney, Kay Elston, Lina Grauslyte, Musarat Hussain, Mandeep Phull, Tatiana Pogreban, Lace Rosaroso, Erika Šalčiūtė, George R. Franke, Joanna Wong, Aparna George, Laura Ortiz-Ruiz de Gordoa, Emily Peasgood, Claire Phillips, Michelle Bates, J Dasgin, Jaspret Gill, Annette Nilsson, James Scriven, Amy Collins, Waqas Khaliq, Estefania Treus Gude, Carlos Castro Delgado, Deborah Dawson, Lijun Ding, Georgia Durrant, Obiageri Ezeobu, Sarah Farnell-Ward, Abiola Harrison, Rebecca Kanu, Susannah Leaver, Elena Maccacari, Soumendu Manna, Romina Pepermans Saluzzio, Joana Queiroz, Tinashe Samakomva, Christine Sicat, Joana Texeira, Edna Fernandes Da Gloria, Ana Lisboa, John Rawlins, Jisha Mathew, Ashley Kinch, William James Hurt, Nirav R. Shah, Victoria Clark, Maria Thanasi, Nikki Yun, Kamal Patel, Sara Bennett, Emma C. Goodwin, Matthew Jackson, Alissa Kent, Clare Tibke, Wiesia Woodyatt, Ahmed F. Zaki, Azmerelda Abraheem, Peter Bamford, Kathryn Cawley, Charlie Dunmore, Maria Faulkner, Rumanah Girach, Helen Jeffrey, Rhianna Jones, Emily London, Imrun Nagra, Farah Nasir, Hannah Sainsbury, Clare Smedley, Tahera Patel, Matthew Smith, Srikanth Chukkambotla, Aayesha Kazi, Janice Hartley, Joseph Dykes, Muhammad Hijazi, Sarah Keith, Meherunnisa Khan, Janet Ryan-Smith, Philippa Springle, Jacqueline Thomas, Nick Truman, Samuel Saad, Dabheoc Coleman, Christopher Fine, Roseanna Matt, Bethan Gay, Jack Dalziel, Syamlan Ali, Drew Goodchild, Rhiannan Harling, Ravi Bhatterjee, Wendy Goddard, Chloe Davison, Stephen Duberly, Jeanette Hargreaves, Rachel Bolton, Miriam Davey, David B.K. Golden, Rebecca Seaman, Shiney Cherian, Sean Cutler, Anne Emma Heron, Anna Roynon-Reed, Tamás Szakmány, Gemma Williams, Owen Richards, Yusuf Cheema, Hollie Brooke, Sarah Buckley, Jose Cebrian Suarez, Ruth Charlesworth, Karen Hansson, John W. Norris, Alice Poole, Alastair Rose, Rajdeep Sandhu, Brendan Sloan, Elizabeth Smithson, Muthu Thirumaran, Veronica Wagstaff, Alexandra Metcalfe, Mark Brunton, Jess Caterson, Holly Coles, Matthew Frise, Sabi Gurung, Nicola Jacques, Liza Keating, Emma Tilney, Shauna Bartley, Parminder Bhuie, Sian Gibson, Amanda Lyle, Fiona McNeela, Jayachandran Radhakrishnan, Alistair Hughes, Bryan Yates, Jessica Reynolds, Helen Campbell, Maria Thompsom, Steve Dodds, Stacey Duffy, Sandra Greer, Karen Shuker, Ascanio Tridente, Reena Khade, Ashok Sundar, George Tsinaslanidis, Isobel Birkinshaw, J. W. S. Carter, Kate Howard, Joanne Ingham, Rosie Joy, Harriet Pearson, Samantha Roche, Zoë Scott, Hollie Bancroft, Mary Bellamy, Margaret Carmody, Jacqueline Daglish, Faye Moore, Joanne Rhodes, Mirriam Sangombe, Salma Kadiri, James Scriven, Maria Croft, Ian White, Victoria Frost, Maia Aquino, Rajeev Jha, Vinodh Krishnamurthy, Lai Lim, Li Hong Idris Lim, Edward Combes, Teishel Joefield, Sonja Monnery, Valerie Beech, Sallyanne Trotman, Christine Almaden-Boyle, Pauline Austin, Louise Cabrelli, Stephen Cole, Matt Casey, Susan Chapman, Clare Whyte, Yolanda Baird, Aaron Butler, Indra Chadbourn, Linda Folkes, Heather Fox, Amy Gardner, Raquel Gomez, Gillian Hobden, Luke Hodgson, Kirsten King, Michael Margarson, Tim Martindale, Emma Meadows, Dana Raynard, Yvette Thirlwall, David Helm, Jordi Margalef, Kristine Criste, Rebecca Cusack, Kim Golder, Hannah Golding, Oliver Jones, Samantha Leggett, Michelle Male, Martyna Marani, Kirsty Prager, Toran Williams, Belinda Roberts, Karen Salmon, Peter Anderson, Katie E. Archer, Karen Austin, Caroline Davis, Alison Durie, Olivia Kelsall, Jessica Thrush, Charlie Vigurs, Laura Wild, Hannah-Louise Wood, Helen Tranter, Alison Harrison, Nicholas Cowley, Michael McAlindon, Andrew Burtenshaw, Stephen Digby, Emma Low, Aled Morgan, Naiara Cother, Tobias Rankin, Sarah Clayton, Alex McCurdy, Cecilia Ahmed, Balvinder Baines, Sarah Clamp, Julie Colley, Risna Haq, Anne Hayes, Jonathan Hulme, Samia Hussain, Sibet Joseph, Rita Kumar, Zahira Maqsood, Manjit Purewal, Leonie Benham, Zena Bradshaw, Joanna Brown, Melanie Caswell, Jason Cupitt, Sarah Melling, Stephen Preston, Nicola Slawson, Emma Stoddard, Scott Warden, Bethan Deacon, Ceri Lynch, Carla Pothecary, L Roche, Gwenllian Sera Howe, Jayaprakash Singh, Keri Turner, Hannah Ellis, Natalie Stroud, Jodie Hunt, Joy Dearden, Emma Dobson, A. D. Drummond, Michelle Mulcahy, Sheila Munt, Gráinne O’Connor, Jennifer Philbin, Chloe Rishton, Redmond Tully, Sarah Winnard, Glasgow Royal Infirmary team, Susanne Cathcart, Katharine Duffy, Alex Puxty, Kathryn Puxty, Lynne Turner, Jane Ireland, Gary Semple, Kate Long, Simon Whiteley, Elizabeth Wilby, Bethan Ogg, Amanda Cowton, Andrea Kay, Melanie Kent, Kathryn Potts, Ami Wilkinson, Suzanne Campbell, Ellen Brown, Julie Melville, Jay Naisbitt, Rosane Joseph, Maria Lazo, Olivia Walton, Alan Neal, Peter Alexander, Schvearn Allen, Joanne Bradley-Potts, Craig Brantwood, Jasmine Egan, Timothy Felton, Grace Padden, Luke Ward, Stuart Moss, Susannah Glasgow, Lynn Abel, Michael Brett, Brian Digby, Lisa Gemmell, James Hornsby, Patrick MacGoey, Pauline O’Neil, R. Arlen Price, Natalie Rodden, Kevin Rooney, Radha Sundaram, Nicola Thomson, Bridget Hopkins, James Scriven, Laura Thrasyvoulou, Heather Willis, Martyn Clark, M Coulding, Edward B. Jude, Jacqueline McCormick, Oliver Mercer, Darsh Potla, Hafiz Muhammad Rehman, Heather Savill, Victoria Turner, Charlotte Downes, Kathleen Holding, Katie Riches, Mary A. Hilton, Melanie Hayman, Deepak Subramanian, Priya Daniel, Oluronke Adanini, Nikhil Bhatia, Maines Msiska, Rebecca Collins, Royal Victoria Infirmary team, I Clement', Bijal Patel, Arvind Gulati, Carole Hays, Kimberly Webster, Anne Hudson, Andrea J. Webster, Elaine Stephenson, Louise McCormack, Victoria Slater, Rachel Nixon, Helen Hanson, Maggie Fearby, Sinéad Kelly, Victoria Bridgett, Philip Robinson, Julie Camsooksai, Charlotte Humphrey, Sarah M. Jenkins, Henrik Reschreiter, Beverley Wadams, Yasmin DeAth, Victoria Bastion, Daphene Clarke, Beena David, Harriet Kent, Rachel Lorusso, Gamu Lubimbi, Sophie Murdoch, Melchizedek Penacerrada, Alastair Thomas, Jennifer Valentine, Ana Vochin, Retno Wulandari, Brice Djeugam, Gillian Bell, Katy English, Amro Katary, Louise Wilcox, Michelle Bruce, Karen Connolly, Tracy Duncan, Helen Michael, Gabriella Lindergard, Samuel Hey, Claire Fox, Jordan Alfonso, Laura Jayne Durrans, Jacinta Guerin, Bethan Blackledge, Jade Harris, Martin Hruška, Ayaa Eltayeb, Thomas Lamb, Tracey Hodgkiss, Lisa Cooper, Joanne Rothwell, Aberdeen Royal Infirmary team, Angela Allan, Felicity Anderson, Callum Kaye, Jade Liew, Jasmine Medhora, Teresa Scott, Erin Trumper, Adriana Botello, Liana Lankester, Nikitas Nikitas, Colin Wells, Bethan Stowe, Kayleigh Spencer, Manchester Royal Infirmary team, Craig Brandwood, Lara Smith, Richard Clark, Katie Birchall, Laurel Kolakaluri, Deborah L. Baines, Anila Sukumaran, Elena Apetri, Cathrine Basikolo, Bethan Blackledge, Laura Catlow, Bethan Charles, Paul Dark, Reece Doonan, Jade Harris, Alice Harvey, Daniel Horner, Karen Knowles, Stephanie J. Lee, Diane Lomas, Chloe Lyons, Tracy Marsden, Danielle McLaughlan, Liam McMorrow, Jessica Pendlebury, Jane Perez, Maria Poulaka, Nicola Proudfoot, Melanie Slaughter, Kathryn Slevin, Melanie Taylor, Vicky Thomas, Danielle Walker, Angiy Michael, Matthew Collis, Tracey Cosier, Gemma Millen, Neil Richardson, Natasha Schumacher, Heather Weston, James Rand, Nicola Baxter, Steven Henderson, Sophie Kennedy-Hay, Christopher McParland, Laura Rooney, Malcolm Sim, Gordan McCreath, Bradford Royal Infirmary team, Louise Akeroyd, Shereen Bano, Matt Bromley, Lucy Gurr, Tom Lawton, James P. Morgan, Kirsten Sellick, Deborah Warren, Brian J. Wilkinson, Janet McGowan, Camilla Ledgard, Amelia Stacey, Kate Pye, Ruth Bellwood, Michael J. Bentley, Bristol Royal Infirmary team, Jeremy Bewley, Zoe Garland, Lisa Grimmer, Bethany Gumbrill, Rebekah Johnson, Katie Sweet, Denise Webster, Georgia Efford, Karen Convery, Deirdre Fottrell-Gould, Lisa Hudig, Jocelyn Keshet-Price, Georgina Randell, Katie Stammers, Maria Bokhari, Vanessa Linnett, Rachael Lucas, W McCormick, Jenny Ritzema, Amanda Sanderson, Helen Wild, Anthony Rostron, Alistair Roy, Lindsey Woods, Sarah Cornell, Fiona Wakinshaw, Kimberley Rogerson, Jordan Jarmain, Robert S. Parker, Amie Reddy, Ian Turner-Bone, Laura Wilding, Peter Harding, Hull Royal Infirmary team, C. R. Abernathy, Louise Foster, Andrew Gratrix, Vicky Martinson, Priyai Parkinson, Elizabeth Stones, Llucia Carbral-Ortega, Georgia Bercades, David Brealey, Ingrid Hass, Niall MacCallum, Gladys Martir, Eamon Raith, Anna Reyes, Deborah Smyth, Letizia Zitter, Sarah Benyon, Suzie Marriott, Linda Park, Samantha Keenan, Elizabeth Gordón, Helen R. Quinn, Kizzy Baines, Lenka Cagova, Adama Fofano, Lucie Garner, Helen Holcombe, Sue Mepham, Alice Michael Mitchell, Lucy Mwaura, Krithivasan Praman, Alain Vuylsteke, Julie Zamikula, Bally Purewal, Vanessa Rivers, Stephanie Bell, Hayley Blakemore, Borislava Borislavova, Beverley Faulkner, Emma Gendall, Elizabeth Goff, Kati Hayes, Matt Thomas, Ruth Worner, Kerry Smith, Deanna Stephens, Louise Mew, Esther Mwaura, Richard Stewart, Felicity Williams, Lynn Wren, Sara-Beth Sutherland, Emily Bevan, Jane Martin, Dawn Trodd, Geoff Watson, Caroline Wrey Brown, Olugbenga Akinkugbe, Alasdair Bamford, Emily Beech, Holly Belfield, M. J. Bell, Charlene Davies, Gareth A. Jones, Tara McHugh, Hamza Meghari, Lauran O’Neill, Mark Peters, Samiran Ray, Ana Luisa Tomas, Iona Burn, Geraldine Hambrook, Katarina Manso, Ruth Penn, Pradeep Shanmugasundaram, Julie Tebbutt, Danielle Thornton, Jade Cole, Michelle Davies, Rhys Davies, Donna Duffin, Helen Hill, Ben Player, Emma Thomas, Angharad Williams, Denise Griffin, Nycola Muchenje, McDonald Mupudzi, Richard Partridge, Jo-Anna Conyngham, Rachel Thomas, Mary Wright, Maria Alvarez Corral, Reni Jacob, Cathy Jones, Craig Denmade, Sarah Beavis, Katie Dale, Rachel Gascoyne, Joanne Hawes, Kelly Pritchard, Lesley Stevenson, Amanda Whileman, Patricia Doble, Joanne Hutter, Corinne Pawley, Charmaine Shovelton, Marius Vaida, Deborah Butcher, Susie O’Sullivan, Nicola Butterworth‐Cowin, Norfaizan Ahmad, Joann Barker, Kris Bauchmüller, Sarah Bird, Kay Cawthron, Kate Harrington, Yvonne Jackson, Faith Kibutu, Becky Lenagh, Shamiso Masuko, Gary Mills, Ajay Raithatha, M. D. Wiles, Jayne Willson, Helen Newell, Alison Lye, Lorenza Nwafor, Claire Jarman, Sarah Rowland‐Jones, David Foote, Joby Cole, Roger Thompson, James Watson, Lisa Hesseldon, Irene Macharia, Luke Chetam, Jacqui Smith, Amber Ford, Samantha Anderson, Kathryn Birchall, Kay Housley, Sara E. Walker, L Milner, Helena Hanratty, Helen Trower, Patrick Phillips, Simon Oxspring, B. Donne, Dumfries and Galloway Royal Infirmary team, Catherine Jardine, Dewi Williams, Alasdair Hay, Rebecca C. Flanagan, Gareth Hughes, Scott Latham, Emma McKenna, Jennifer Anderson, Robert Hull, Kat Rhead, Carina Cruz, Natalie Pattison, Rob Charnock, Denise McFarland, Denise Cosgrove, Ashar Ahmed, Anna Morris, Srinivas Jakkula, Arvind Nune, Asifa Ali, Megan Brady, Sam Dale, Annalisa Dance, Lisa Gledhill, Jill Greig, Kathryn Hanson, Kelly Holdroyd, Marie Home, Diane Kelly, Ross Kitson, Lear Matapure, D. Salas y Mélia, Samantha Mellor, Tonicha Nortcliffe, Jez Pinnell, Matthew K. Robinson, Lisa Shaw, Ryan Shaw, Lesley Thomis, Alison Wilson, Tracy Wood, Lee-Ann Bayo, Ekta Merwaha, Tahira Ishaq, Sarah Hanley, Bethan Deacon, Meg Hibbert, Carla Pothecary, Dariusz Tetla, Christopher Woodford, Latha Durga, Gareth Kennard-Holden, Debbie Branney, Jordan Frankham, Sally Pitts, Nigel White, Shondipon Laha, Mark Verlander, Alexandra Williams, Abdelhakim Altabaibeh, Ana Alvaro, Kayleigh Gilbert, Louise Ma, Loreta Mostoles, Chetan Parmar, Kathryn Simpson, Champa Jetha, Lauren Booker, Anezka Pratley, Colene Adams, Anita Agasou, Tracie Arden, Amy Bowes, Pauline Boyle, Mandy Beekes, Heather Button, Nigel Capps, Mandy Carnahan, Anne Carter, Danielle Childs, Denise Donaldson, Kelly Hard, F Hurford, Yasmin Hussain, Ayesha Javaid, James Jones, Sanal Jose, Michael Leigh, Terry Martin, Helen Millward, Nichola Motherwell, Rachel Rikunenko, Jo Stickley, Julie Summers, Louise Ting, Helen Tivenan, Louise Tonks, Rebecca Wilcox, Denise Skinner, Jane Gaylard, Dee Mullan, Julie Newman, Maureen Holland, Natalie Keenan, Marc Lyons, Helen Wassall, Chris Marsh, Mervin Mahenthran, Emma Carter, Thomas Kong, Helen Blackman, Ben Creagh‐Brown, Sinead Donlon, Natalia Michalak-Glinska, Sheila Mtuwa, Veronika Pristopan, Armorel Salberg, Eleanor Smith, Sarah Stone, Charles Piercy, Jerik Verula, D Burda, Rugia Montaser, Lesley Harden, Irving Mayangao, Cheryl Marriott, Paul Bradley, Celia B. Harris, Susan M. Anderson, Eleanor Andrews, Janine Birch, Emma Collins, Kate Hammerton, Ryan O’Leary, Michele Clark, Sarah Purvis, Russell Barber, Claire Hewitt, Annette Hilldrith, Karen Jackson-Lawrence, Sarah Shepardson, Maryanne Wills, Susan Butler, Silvia Tavares, Amy Cunningham, Julia Hindale, Sarwat Arif, Sarah Bean, Karen Burt, Michael Z. Spivey, Carrie Demetriou, Charlotte Eckbad, Sarah Hierons, Lucy Howie, Sarah Mitchard, Lidia Ramos, Alfredo Serrano-Ruiz, Katie White, F. M. Kelly, Daniele Cristiano, Natalie Dormand, Zohreh Farzad, Mahitha Gummadi, Kamal Liyanage, Brijesh Patel, Sara Salmi, Geraldine Sloane, Vicky Thwaites, Mathew Varghese, Anelise Catelan Zborowski, John Allan, Tim Geary, J. Graeme Houston, A.W. Meikle, Peter C. O’Brien, Miranda Forsey, Agilan Kaliappan, Anne Nicholson, Joanne Riches, Mark Vertue, Elizabeth Allan, Kate Darlington, Ffyon Davies, Jack Easton, Sumit Kumar, Richard Lean, Daniel Menzies, Richard Pugh, Xinyi Qiu, Llinos Davies, Hannah Williams, Jeremy Scanlon, Gwyneth Davies, Callum Mackay, Joanne Lewis, Stephanie Rees, Metod Oblak, Monica Popescu, Mini Thankachen, Royal Lancaster Infirmary team, Andrew Higham, Kerry Simpson, Jayne Craig, Rosie Baruah, Sheila Morris, Susie Ferguson, Amy Shepherd, Luke Moore, Marcela P. Vizcaychipi, Laura Gomes de Almeida Martins, Jaime Carungcong, Inthakab Ali Mohamed Ali, Karen Beaumont, Mark Blunt, Zoe Coton, Hollie Curgenven, Mohamed Elsaadany, Kay Fernandes, Sameena Mohamed Ally, Harini Rangarajan, Varun Sarathy, Sivarupan Selvanayagam, Dave Vedage, Matthew White, Mandy Gill, Paul Paul, Valli Ratnam, Sarah Shelton, Inez Wynter, Siobhain Carmody, Valérie Page, Claire Beith, Karen Black, Suzanne Clements, Alan Morrison, Dominic Strachan, Margaret Taylor, Michelle Clarkson, Stuart D’Sylva, K. Norman, F. C. Auld, Joanne Donnachie, Ian Edmond, Lynn Prentice, Nikole Runciman, Dario Salutous, Lesley Symon, Anne Todd, Patricia Turner, Abigail Short, Laura Sweeney, Euan Murdoch, Dhaneesha Senaratne, Michaela Hill, Thogulava Kannan, Laura Wild, Rikki Crawley, Abigail Crew, Mishell Cunningham, Allison Daniels, Laura Harrison, Susan Hope, Ken Inweregbu, Siân Jones, Nicola Lancaster, Jamie Matthews, Alice Nicholson, Gemma Wray, Helen Langton, Rachel Prout, Malcolm Watters, Catherine Novis, Anthony Barron, Ciara Collins, Sundeep Kaul, Heather Passmore, Claire Prendergast, Anna Reed, Paula Rogers, Rajvinder Shokkar, Meriel Woodruff, Hayley Middleton, Oliver Polgar, Claire M. Nolan, Vicky Thwaites, Kanta Mahay, Dawn Collier, Anil Hormis, Victoria Maynard, Cheryl Graham, Rachel Walker, Ysbyty Gwynedd team, Ellen Knights, Alicia Price, Alice Thomas, Chris Thorpe, Teresa Behan, Caroline Burnett, Jonathan Hatton, Elaine Heeney, Atideb Mitra, Maria Newton, Rachel E. Pollard, Rachael Stead, Vishal Amin, Elena Anastasescu, Vikram Anumakonda, Komala Karthik, Rizwana Kausar, Karen Reid, Jacqueline Smith, Janet Imeson-Wood, Alison Brown, Vikki Crickmore, Gabor Debreceni, Joy Wilkins, Liz Nicol, Waqas Khaliq, Rosie Reece-Anthony, Mark Birt, Alison Ghosh, Emma Williams, Louise Allen, Eva Beranová, Nikki Crisp, Joanne Deery, Tracy Hazelton, Alicia Knight, Carly Price, Sorrell Tilbey, Salah Turki, Sharon Turney, Royal Albert Edward Infirmary team, Joshua Cooper, Cheryl Finch, Sarah Liderth, Alison Quinn, Natalia Waddington, Tina Coventry, Susan A. Fowler, Michael MacMahon, Amanda McGregor, Anne Cowley, Judith Highgate, Cumberland Infirmary team, Alison Brown, Jane Gregory, Susan O’Çonnell, Timothy F. Smith, Luigi Barberis, Shameer Gopal, Nichola Harris, Victoria Lake, Stella Metherell, Elizabeth J. Radford, Amelia Daniel, Joanne Finn, Rajnish Saha, Nikki White, Amy Easthope, Phil Donnison, Fiona Trim, Beena Eapen, Jenny Birch, Laura Bough, Josie Goodsell, Rebecca Tutton, Patricia Williams, Sarah Williams, Barbara Winter-Goodwin, Ailstair Nichol, Kathy Brickell, Michelle Smyth, Lorna Murphy, Samantha Coetzee, Alistair Gales, Igor Otahal, Meena Raj, Craig Sell, Paula Hilltout, Jayne Evitts, Amanda Tyler, Joanne Waldron, Kate Beesley, Sarah Board, Agnieszka Kubisz-Pudelko, Alison Lewis, Jess Perry, Lucy Pippard, Di Wood, Clare Buckley, Leicester Royal Infirmary team, Peter Barry, Neil Flint, Patel Rekha, Dawn Hales, Lara Bunni, Claire Jennings, Monica Latif, Rebecca Marshall, Gayathri Subramanian, Peter J. McGuigan, Christopher W. Wasson, Stephanie Finn, Jackie Green, Erin Collins, Bernadette King, Andy Campbell, Sara Smuts, Joseph Duffield, Oliver Smith, Lewis Mallon, Claire Watkins, Liam Botfield, Joanna Butler, Catherine Dexter, Jo Fletcher, Atul Garg, Aditya Kuravi, Poonam Ranga, Emma Virgilio, Zakaula Belagodu, Bridget Fuller, Anca Gherman, Olumide Olufuwa, Remi Paramsothy, Carmel Stuart, Naomi Oakley, Charlotte Kamundi, David Tyl, Katy Collins, Pedro Silva, June S. Taylor, Laura King, Charlotte Coates, Maria Crowley, Phillipa Wakefield, Jane Beadle, Laura Johnson, Janet Sargeant, Madeleine Anderson, Ailbhe Brady, Rebekah Chan, Jeff Little, Shane McIvor, Helena Prady, Helen Whittle, Bijoy Mathew, Ben Attwood, Penny Parsons, Geraldine Ward, Pamela Bremmer, West Joe, B. L. Tracy, Ruddy Jim, Ellie Davies, L Roche, Sonia Sathe, Catherine Dennis, Alastair McGregor, Victoria Parris, Sinduya Srikaran, Anisha Sukha, Rachael Campbell, Noreen Clarke, Jonathan Whiteside, Mairi Mascarenhas, Avril Donaldson, Joanna Matheson, Fiona Barrett, Marianne O’Hara, Laura Okeefe, Clare Bradley, Christine Eastgate-Jackson, Helder Filipe, Daniel Martín, Amitaa Maharajh, Sara Mingo Garcia, Glykeria Pakou, Mark De Neef, Kathy Dent, Elizabeth Horsley, Muhammad Nauman Akhtar, Sandra Pearson, Dorota Potoczna, Sue Spencer, Melanie Clapham, Rosemary Harper, Una Poultney, Polly Rice, Timothy F. Smith, Rachel Mutch, Luigi Barberis, Lisa Armstrong, Hayley Bates, Emma Dooks, Fiona Farquhar, Brigid Hairsine, Chantal McParland, Sophie Packham, Rehana Bi, Barney Scholefield, Lydia Ashton, Linsha George, Sophie Twiss, David J. Wright, Manish Chablani, Amy Kirkby, Kimberley Netherton, Kim Davies, Linda O’Brien, Zohra Omar, Igor Otahal, Emma Perkins, Tracy R. Lewis, Isobel Sutherland, Karen E. A. Burns, Andrew Higham, Ben Chandler, Kerry Elliott, Janine Mallinson, Alison E. Turnbull, Prisca Gondo, Bernard Hadebe, Abdul Kayani, Bridgett Masunda, Taya Anderson, Daniel B. Hawcutt, Laura O’Malley, Laura Rad, Naomi Rogers, Paula Saunderson, Kathryn Allison, Deborah Afolabi, Jennifer Whitbread, Dawn Jones, Rachael Dore, Matthew Halkes, Pauline Mercer, Lorraine Thornton, Joy Dawson, Sweyn Garrioch, Melanie Tolson, Jonathan Aldridge, Ritoo Kapoor, David Loader, Karen J. Castle, Sally Humphreys, Ruth Tampsett, Katherine Mackintosh, Amanda Ayers, Dean Harris, Julie North, Suzanne Allibone, Roman Genetu, Vidya Kasipandian, Amit R. Patel, Ainhi Mac, Anthony Murphy, Parisa Mahjoob, Roonak Nazari, Lucy Worsley, Andrew Fagan, Thomas Bemand, Ethel Black, Arnold Dela Rosa, Ryan Howle, Shaman Jhanji, Ravishankar Rao Baikady, Kate Tatham, Benjamin Thomas, Dina Bell, Rosalind Boyle, Katie M. Douglas, Lynn Glass, Emma Lee, Liz Lennon, Austin Rattray, Abigail Taylor, Rachel Anne Hughes, Helen Thomas, A.R. Rees, Michaela Dušková, Janet Phipps, Suzanne Brooks, Michelle Edwards, Victoria Parris, Sheena Quaid, Ekaterina Watson, Adam Brayne, Emma Fisher, Jane Hunt, Peter K. Jackson, Duncan Kaye, Nicholas Love, Juliet Parkin, Victoria Tuckey, Lynne van Koutrik, Sasha Carter, Benedict Andrew, L. Findlay, Katie Adams, Jen Service, Alison S. 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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 colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.