1. Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity
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Fallerini, Chiara, Picchiotti, Nicola, Baldassarri, Margherita, Zguro, Kristina, Daga, Sergio, Fava, Francesca, Benetti, Elisa, Amitrano, Sara, Bruttini, Mirella, Palmieri, Maria, Croci, Susanna, Lista, Mirjam, Beligni, Giada, Valentino, Floriana, Meloni, Ilaria, Tanfoni, Marco, Minnai, Francesca, Colombo, Francesca, Cabri, Enrico, Fratelli, Maddalena, Gabbi, Chiara, Mantovani, Stefania, Frullanti, Elisa, Gori, Marco, Crawley, Francis P, Butler-Laporte, Guillaume, Richards, Brent, Zeberg, Hugo, Lipcsey, Miklos, Hultström, Michael, Ludwig, Kerstin U, Schulte, Eva C, Pairo-Castineira, Erola, Baillie, John Kenneth, Schmidt, Axel, Frithiof, Robert, Mari, Francesca, Renieri, Alessandra, Furini, Simone Simone Furini, Francesca, Montagnani, Mario, Tumbarello, Ilaria, Rancan, Massimiliano, Fabbiani, Barbara, Rossetti, Laura, Bergantini, Miriana, D'Alessandro, Paolo, Cameli, David, Bennett, Federico, Anedda, Simona, Marcantonio, Sabino, Scolletta, Federico, Franchi, Maria Antonietta Mazzei, Susanna, Guerrini, Edoardo, Conticini, Luca, Cantarini, Bruno, Frediani, Danilo, Tacconi, Chiara Spertilli Raffaelli, Marco, Feri, Alice, Donati, Raffaele, Scala, Luca, Guidelli, Genni, Spargi, Marta, Corridi, Cesira, Nencioni, Leonardo, Croci, Gian Piero Caldarelli, Maurizio, Spagnesi, Davide, Romani, Paolo, Piacentini, Maria, Bandini, Elena, Desanctis, Silvia, Cappelli, Anna, Canaccini, Agnese, Verzuri, Valentina, Anemoli, Manola, Pisani, Agostino, Ognibene, Alessandro, Pancrazzi, Maria, Lorubbio, Massimo, Vaghi, Antonella, D 'Arminio Monforte, Federica Gaia Miraglia, Mario, U Mondelli, Massimo, Girardis, Sophie, Venturelli, Stefano, Busani, Andrea, Cossarizza, Andrea, Antinori, Alessandra, Vergori, Arianna, Emiliozzi, Stefano, Rusconi, Matteo, Siano, Arianna, Gabrieli, Agostino, Riva, Daniela, Francisci, Elisabetta, Schiaroli, Francesco, Paciosi, Andrea, Tommasi, Pier Giorgio Scotton, Francesca, Andretta, Sandro, Panese, Stefano, Baratti, Renzo, Scaggiante, Francesca, Gatti, Saverio Giuseppe Parisi, Francesco, Castelli, Eugenia, Quiros-Roldan, Melania Degli Antoni, Isabella, Zanella, Matteo Della Monica, Carmelo, Piscopo, Mario, Capasso, Roberta, Russo, Immacolata, Andolfo, Achille, Iolascon, Giuseppe, Fiorentino, Massimo, Carella, Marco, Castori, Filippo, Aucella, Pamela, Raggi, Rita, Perna, Matteo, Bassetti, Antonio Di Biagio, Maurizio, Sanguinetti, Luca, Masucci, Alessandra, Guarnaccia, Serafina, Valente, Oreste De Vivo, Gabriella, Doddato, Rossella, Tita, Annarita, Giliberti, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Valentina, Perticaroli, Francesca, Ariani, Miriam Lucia Carriero, Laura Di Sarno, Diana, Alaverdian, Elena, Bargagli, Marco, Mandalà, Alessia, Giorli, Lorenzo, Salerni, Patrizia, Zucchi, Pierpaolo, Parravicini, Elisabetta, Menatti, Tullio, Trotta, Ferdinando, Giannattasio, Gabriella, Coiro, Fabio, Lena, Leonardo Gianluca Lacerenza, Domenico, A Coviello, Cristina, Mussini, Enrico, Martinelli, Sandro, Mancarella, Luisa, Tavecchia, Mary Ann Belli, Lia, Crotti, Gianfranco, Parati, Maurizio, Sanarico, Francesco, Raimondi, Filippo, Biscarini, Alessandra, Stella, Marco, Rizzi, Franco, Maggiolo, Diego, Ripamonti, Claudia, Suardi, Tiziana, Bachetti, Maria Teresa La Rovere, Simona, Sarzi-Braga, Maurizio, Bussotti, Katia, Capitani, Simona, Dei, Sabrina, Ravaglia, Rosangela, Artuso, Elena, Andreucci, Giulia, Gori, Angelica, Pagliazzi, Erika, Fiorentini, Antonio, Perrella, Francesco, Bianchi, Paola, Bergomi, Emanuele, Catena, Riccardo, Colombo, Sauro, Luchi, Giovanna, Morelli, Paola, Petrocelli, Sarah, Iacopini, Sara, Modica, Silvia, Baroni, Francesco Vladimiro Segala, Francesco, Menichetti, Marco, Falcone, Giusy, Tiseo, Chiara, Barbieri, Tommaso, Matucci, Grassi, Davide, Ferri, Claudio, Marinangeli, Franco, Brancati, Francesco, Antonella, Vincenti, Valentina, Borgo, Lombardi, Stefania, Mirco, Lenzi, Massimo Antonio Di Pietro, Francesca, Vichi, Benedetta, Romanin, Letizia, Attala, Cecilia, Costa, Andrea, Gabbuti, Menè, Roberto, Umberto, Zuccon, Lucia, Vietri, Stefano, Ceri, Pietro, Pinoli, Patrizia, Casprini, Giuseppe, Merla, Gabriella Maria Squeo, Marcello, Maffezzoni, Raffaele, Bruno, Marco, Vecchia, Marta, Colaneri, Serena, Ludovisi, Yanara, Marincevic-Zuniga, Jessica, Nordlund, Tomas, Luther, Anders, Larsson, Katja Hanslin Anna Gradin, Sarah, Galien, Sara Bulow Anderberg, Jacob, Rosén, Sten, Rubertsson, Hugo, Zeberg, Robert, Frithiof, Miklós, Lipcsey, Michael, Hultström, Sara Clohisey Peter Horby, Johnny, Millar, Julian, Knight, Hugh, Montgomery, David, Maslove, Lowell, Ling, Alistair, Nichol, Charlotte, Summers, Tim, Walsh, Charles, Hinds, Malcolm, G Semple, Peter J, M Openshaw, Manu, Shankar-Hari, Antonia, Ho, Danny, Mcauley, Chris, Ponting, Kathy, Rowan, J Kenneth Baillie, Fiona, Griffiths, Wilna, Oosthuyzen, Jen, Meikle, Paul, Finernan, James, Furniss, Ellie, Mcmaster, Andy, Law, Sara, Clohisey, Trevor, Paterson, Tony, Wackett, Ruth, Armstrong, Lee, Murphy, Angie, Fawkes, Richard, Clark, Audrey, Coutts, Lorna, Donnelly, Tammy, Gilchrist, Katarzyna, Hafezi, Louise, Macgillivray, Alan, Maclean, Sarah, Mccafferty, Kirstie, Morrice, Jane, Weaver, Ceilia, Boz, Ailsa, Golightly, Mari, Ward, Hanning, Mal, Helen, Szoor-McElhinney, Adam, Brown, Ross, Hendry, Andrew, Stenhouse, Louise, Cullum, Dawn, Law, Sarah, Law, Rachel, Law, Max Head Fourman, Maaike, Swets, Nicky, Day, Filip, Taneski, Esther, Duncan, Marie, Zechner, Nicholas, Parkinson, Erola, Pairo-Castineira, Lucija, Klaric, Andrew, D Bretherick, Konrad, Rawlik, Dorota, Pasko, Susan, Walker, Nick, Parkinson, Clark, D Russell, Anne, Richmond, Elvina, Gountouna, David, Harrison, Wang, Bo, Yang, Wu, Alison, Meynert, Athanasios, Kousathanas, Loukas, Moutsianas, Zhijian, Yang, Ranran, Zhai, Chenqing, Zheng, Graeme, Grimes, Jonathan, Millar, Barbara, Shih, Jian, Yang, Xia, Shen, Chris, P Ponting, Albert, Tenesa, Andrew, Law, Veronique, Vitart, James, F Wilson, Collier, D, Wood, S, Zak, A, Borra, C, Matharu, M, May, P, Alldis, Z, Mitchelmore, O, Bowles, R, Easthorpe, A, Bibi, F, Lancoma-Malcolm, I, Gurasashvili, J, Pheby, J, Shiel, J, Bolton, M, Patel, M, Taylor, M, Zongo, O, Ebano, P, Harding, P, Astin-Chamberlain, R, Choudhury, Y, Cox, A, Kallon, D, Burton, M, Hall, R, Blowes, S, Prime, Z, Biddle, J, Prysyazhna, O, Newman, T, Tierney, C, Kassam, J, Shankar-Hari, M, Ostermann, M, Campos, S, Bociek, A, Lim, R, Grau, N, O Jones, T, Whitton, C, Marotti, M, Arbane, G, Bonner, S, Hugill, K, Reid, J, Welters, I, Waugh, V, Williams, K, Shaw, D, J Fernandez Roman, M Lopez Martinez, Johnson, E, Waite, A, Johnson, B, Hamilton, O, Mulla, S, Mcphail, M, Smith, J, K Baillie, J, Barclay, L, Hope, D, Mcculloch, C, Mcquillan, L, Clark, S, Singleton, J, Priestley, K, Rea, N, Callaghan, M, Campbell, R, Andrew, G, Marshall, L, Mckechnie, S, Hutton, P, Bashyal, A, Davidson, N, Summers, C, Polgarova, P, Stroud, K, Pathan, N, Elston, K, Agrawal, S, Battle, C, Newey, L, Rees, T, Harford, R, Brinkworth, E, Williams, M, Murphy, C, White, I, Croft, M, Bandla, N, Gellamucho, M, Tomlinson, J, Turner, H, Davies, M, Quinn, A, Hussain, I, Thompson, C, Parker, H, Bradley, R, Griffiths, R, Scriven, J, Gill, J, Puxty, A, Cathcart, S, Salutous, D, Turner, L, Duffy, K, Puxty, K, Joseph, A, Herdman-Grant, R, Simms, R, Swain, A, Naranjo, A, Crowe, R, Sollesta, K, Loveridge, A, Baptista, D, Morino, E, Davey, M, Golden, D, Jones, J, J Moreno Cuesta, Haldeos, A, Bakthavatsalam, D, Vincent, R, Elhassan, M, Xavier, K, Ganesan, A, Purohit, D, Abdelrazik, M, Morgan, J, Akeroyd, L, Bano, S, Warren, D, Bromley, M, Sellick, K, Gurr, L, Wilkinson, B, Nagarajan, V, Szedlak, P, Cupitt, J, Stoddard, E, Benham, L, Preston, S, Slawson, N, Bradshaw, Z, Brown, J, Caswell, M, Smelling, Bamford, P, Faulkner, M, Cawley, K, Jeffrey, H, London, E, Sainsbury, H, Nagra, I, Nasir, F, Dunmore, Ce, Jones, R, Abraheem, A, Al-Moasseb, M, Girach, R, Brantwood, C, Alexander, P, Bradley-Potts, J, Allen, S, Felton, T, Manna, S, Farnell-Ward, S, Leaver, S, Queiroz, J, Maccacari, E, Dawson, D, C Castro Delgado, R Pepermans Saluzzio, Ezeobu, O, Ding, L, Sicat, C, Kanu, R, Durrant, G, Texeira, J, Harrison, A, Samakomva, T, Willis, H, Hopkins, B, Thrasyvoulou, L, Jackson, M, Zaki, A, Tibke, C, Bennett, S, Woodyatt, W, Kent, A, Goodwin, E, Brandwood, C, Clark, R, Smith, L, Rooney, K, Thomson, N, Rodden, N, Hughes, E, Mcglynn, D, Clark, C, Clark, P, Abel, L, Sundaram, R, Gemmell, L, Brett, M, Hornsby, J, Macgoey, P, Price, R, Digby, B, O'Neil, P, Mcconnell, P, Henderson, P, Henderson, S, Sim, M, Kennedy-Hay, S, Mcparland, C, Rooney, L, Baxter, N, Pogson, D, Rose, S, Daly, Z, Brimfield, L, K Phull, M, Hussain, M, Pogreban, T, Rosaroso, L, E Salciute, L Grauslyte, Brealey, D, Wraith, E, Maccallum, N, Bercades, G, Hass, I, Smyth, D, Reyes, A, Martir, G, D Clement, I, Webster, K, Hays, C, Gulati, A, Hodgson, L, Margarson, M, Gomez, R, Baird, Y, Thirlwall, Y, Folkes, L, Butler, A, Meadows, E, Moore, S, Raynard, D, Fox, H, Riddles, L, King, K, Kimber, S, Hobden, G, Mccarthy, A, Cannons, V, Balagosa, I, Chadbourn, I, Gardner, A, Horner, D, Mclaughlanv, D, Charles, B, Proudfoot, N, Marsden, T, L Mc Morrow, Blackledge, B, Pendlebury, J, Harvey, A, Apetri, E, Basikolo, C, Catlow, L, Doonan, R, Knowles, K, Lee, S, Lomas, D, Lyons, C, Perez, J, Poulaka, M, Slaughter, M, Slevin, K, Thomas, V, Walker, D, Harris, J, Drummond, A, Tully, R, Dearden, J, Philbin, J, Munt, S, Rishton, C, O'Connor, G, Mulcahy, M, Dobson, E, Cuttler, J, Edward, M, Rose, A, Sloan, B, Buckley, S, Brooke, H, Smithson, E, Charlesworth, R, Sandu, R, Thirumaran, M, Wagstaff, V, J Cebrian Suarez, Kaliappan, A, Vertue, M, Nicholson, A, Riches, J, Solesbury, A, Kittridge, L, Forsey, M, Maloney, G, Cole, J, Davies, R, Hill, H, Thomas, E, Williams, A, Duffin, D, Player, B, Radhakrishnan, J, Gibson, S, Lyle, A, Mcneela, F, Patel, B, Gummadi, M, Sloane, G, Dormand, N, Salmi, S, Farzad, Z, Cristiano, D, Liyanage, K, Thwaites, V, Varghese, M, Meredith, M, Mills, G, Willson, J, Harrington, K, Lenagh, B, Cawthron, K, Masuko, S, Raithatha, A, Bauchmuller, K, Ahmad, N, Barker, J, Jackson, Y, Kibutu, F, Bird, S, Watson, G, Martin, J, Bevan, E, C Wrey Brown, Trodd, D, English, K, Bell, G, Wilcox, L, Katary, A, Gopal, S, Lake, V, Harris, N, Metherell, S, Radford, E, Moore, F, Bancroft, H, Daglish, J, Sangombe, M, Carmody, M, Rhodes, J, Bellamy, M, Garg, A, Kuravi, A, Virgilio, E, Ranga, P, Butler, J, Botfield, L, Dexter, C, Fletcher, J, Shanmugasundaram, P, Hambrook, G, Burn, I, Manso, K, Thornton, D, Tebbutt, J, Penn, R, Hulme, J, Hussain, S, Maqsood, Z, Joseph, S, Colley, J, Hayes, A, Ahmed, C, Haque, R, Clamp, S, Kumar, R, Purewal, M, Baines, B, Frise, M, Jacques, N, Coles, H, Caterson, J, S Gurung Rai, Brunton, M, Tilney, E, Keating, L, Walden, A, Antcliffe, D, Gordon, A, Templeton, M, Rojo, R, Banach, D, S Sousa Arias, Fernandez, Z, Coghlan, P, Williams, D, Jardine, C, Bewley, J, Sweet, K, Grimmer, L, Johnson, R, Garland, Z, Gumbrill, B, Phillips, C, L Ortiz-Ruiz de Gordoa, Peasgood, E, Tridente, A, K Shuker, S Greer, Lynch, C, Pothecary, C, Roche, L, Deacon, B, Turner, K, Singh, J, G Sera Howe, Paul, P, Gill, M, Wynter, I, Ratnam, V, Shelton, S, Naisbitt, J, Melville, J, Baruah, R, Morrison, S, Mcgregor, A, Parris, V, Mpelembue, M, Srikaran, S, Dennis, C, Sukha, A, Verlande, M, Holding, K, Riches, K, Downes, C, Swan, C, Rostron, A, Roy, A, Woods, L, Cornell, S, Wakinshaw, F, Creagh-Brown, B, Blackman, H, Salberg, A, Smith, E, Donlon, S, Mtuwa, S, Michalak-Glinska, N, Stone, S, Beazley, C, Pristopan, V, Nikitas, N, Lankester, L, Wells, C, S Raj, A, Fletcher, K, Khade, R, Tsinaslanidis, G, Mcmahon, M, Fowler, S, Coventry, T, Stewart, R, Wren, L, Mwaura, E, Mew, L, Scaletta, D, Williams, F, Inweregbu, K, Lancaster, N, Cunningham, M, Daniels, A, Harrison, L, Hope, S, Jones, S, Crew, A, Wray, G, Matthews, J, Crawley, R, Carter, J, Birkinshaw, I, Ingham, J, Scott, Z, Howard, K, Joy, R, Roche, S, Clark, M, Purvis, S, Morrison, A, Strachan, D, Clements, S, Black, K, Parmar, C, Altabaibeh, A, Simpson, K, Mostoles, L, Gilbert, K, L, Ma, Alvaro, A, Thomas, M, Faulkner, B, Worner, R, Hayes, K, Gendall, E, Blakemore, H, Borislavova, B, Goff, E, Vuylsteke, A, Mwaura, L, Zamikula, J, Garner, L, Mitchell, A, Mepham, S, Cagova, L, Fofano, A, Holcombe, H, Praman, K, Szakmany, T, E Heron, A, Cherian, S, Cutler, S, Roynon-Reed, A, Randell, G, Convery, K, K Stammers, D Fottrell-Gould, Hudig, L, Keshet-Price, J, Peters, M, O'Neill, L, Ray, S, Belfield, H, Mchugh, T, Jones, G, Akinkugbe, O, Tomas, A, Abaleke, E, Beech, E, Meghari, H, Yussuf, S, Bamford, A, Hairsine, B, Dooks, E, Farquhar, F, Packham, S, Bates, H, Armstrong, L, Kaye, C, Allan, A, Medhora, J, Liew, J, Botello, A, Anderson, F, Cusack, R, Golding, H, Prager, K, Williams, T, Leggett, S, Golder, K, Male, M, Jones, O, Criste, K, Marani, M, Anumakonda, V, Amin, V, Karthik, K, Kausar, R, Anastasescu, E, Reid, K, Jacqui, M, Hormis, A, Walker, R, Duncan, T, Uriel, A, Ustianowski, A, T-Michael, H, Bruce, M, Connolly, K, Smith, K, Partridge, R, Griffin, D, Mcdonald, M, Muchenje, N, Martin, D, Filipe, H, Eastgate, C, Jackson, C, Gratrix, A, Foster, L, Martinson, V, Stones, E, Caroline, Abernathy, Parkinson, P, Reed, A, Prendergast, C, Rogers, P, Woodruff, M, Shokkar, R, Kaul, S, Barron, A, Collins, C, Beavis, S, Whileman, A, Dale, K, Hawes, J, Pritchard, K, Gascoyne, R, Stevenson, L, Jha, R, Lim, L, Krishnamurthy, V, Parker, R, Turner-Bone, I, Wilding, L, Reddy, A, Whiteley, S, Wilby, E, Howcroft, C, Aspinwall, A, Charlton, S, Ogg, B, Menzies, D, Pugh, R, Allan, E, Lean, R, Davies, F, Easton, J, Qiu, X, Kumar, S, Darlington, K, Houston, G, O'Brien, P, Geary, T, Allan, J, Meikle, A, Hughes, G, Balasubramaniam, M, Latham, S, Mckenna, E, Flanagan, R, Sathe, S, Davies, E, Chablani, M, Kirkby, A, Netherton, K, Archer, S, Yates, B, Ashbrook-Raby, C, Cole, S, Casey, M, Cabrelli, L, Chapman, S, Austin, P, Hutcheon, A, Whyte, C, Almaden-Boyle, C, Pattison, N, Cruz, C, Vochin, A, Kent, H, Thomas, A, Murdoch, S, David, B, Penacerrada, M, Lubimbi, G, Bastion, V, Wulandari, R, Valentine, J, Clarke, D, Serrano-Ruiz, A, Hierons, S, Ramos, L, Demetriou, C, Mitchard, S, White, K, White, N, Pitts, S, Branney, D, Frankham, J, Watters, M, Langton, H, Prout, R, Page, V, Varghes, T, Cowton, A, Kay, A, Potts, K, Birt, M, Kent, M, Wilkinson, A, Jude, E, Turner, V, Savill, H, Mccormick, J, Coulding, M, Siddiqui, S, Mercer, O, Rehman, H, Potla, D, Capps, N, Donaldson, D, Button, H, Martin, T, Hard, K, Agasou, A, Tonks, L, Arden, T, Boyle, P, Carnahan, M, Strickley, J, Adams, C, Childs, D, Rikunenko, R, Leigh, M, Breekes, M, Wilcox, R, Bowes, A, Tiveran, H, Hurford, F, Summers, J, Carter, A, Hussain, Y, Ting, L, Javaid, A, Motherwell, N, Moore, H, Millward, H, Jose, S, Schunki, N, Noakes, A, Clulow, C, Sadera, G, Jacob, R, Jones, C, Blunt, M, Coton, Z, Curgenven, H, S Mohamed Ally, Beaumont, K, Elsaadany, M, Fernandes, K, I Ali Mohamed Ali, Rangarajan, H, Sarathy, V, Selvanayagam, S, Vedage, D, White, M, Smith, M, Truman, N, Chukkambotla, S, Keith, S, Cockerill-Taylor, J, Ryan-Smith, J, Bolton, R, Springle, P, Dykes, J, Thomas, J, Khan, M, T Hijazi, M, Massey, E, Croston, G, Reschreiter, H, Camsooksai, J, Patch, S, Jenkins, S, Humphrey, C, Wadams, B, Bhatia, N, Msiska, M, Adanini, O, Attwood, B, Parsons, P, Tatham, K, Jhanji, S, Black, E, A Dela Rosa, Howle, R, Thomas, B, Bemand, T, Raobaikady, R, Saha, R, Staines, N, Daniel, A, Finn, J, Hutter, J, Doble, P, Shovelton, C, Pawley, C, Kannan, T, Hill, M, Combes, E, Monnery, S, Joefield, T, Popescu, M, Thankachen, M, Oblak, M, Little, J, Mcivor, S, Brady, A, Whittle, H, Prady, H, Chan, R, Ahmed, A, Morris, A, Gibson, C, Gordon, E, Keenan, S, Quinn, H, Benyon, S, Marriott, S, Zitter, L, Park, L, Baines, K, Lyons, M, Holland, M, Keenan, N, Young, M, Garrioch, S, Dawson, J, Tolson, M, Scholefield, B, R, Bi, Richardson, N, Schumacher, N, Cosier, T, Millen, G, Higham, A, Turki, S, Allen, L, Crisp, N, Hazleton, T, Knight, A, Deery, J, Price, C, Turney, S, Tilbey, S, Beranova, E, Wright, D, Georg, L, Twiss, S, Wadd, S, Postlethwaite, K, Gondo, P, Masunda, B, Kayani, A, Hadebe, B, Whiteside, J, Clarke, N, Donnison, P, Trim, F, Leadbitter, I, Butcher, D, O'Sullivan, S, Purewal, B, Bell, S, Rivers', V, O'Leary, R, Birch, J, Collins, E, Anderson, S, Hammerton, K, Andrews, E, Burns, K, Edmond, I, Todd, A, Donnachie, J, Turner, P, Prentice, L, Symon, L, Runciman, N, Auld, F, Halkes, M, Mercer, P, Thornton, L, Debreceni, G, Wilkins, J, Brown, A, Crickmore, V, Subramanian, G, Marshall, R, Jennings, C, Latif, M, Bunni, L, Spivey, M, Bean, S, Burt, K, Linnett, V, Ritzema, J, Sanderson, A, Mccormick, W, Bokhari, M, Kapoor, R, Loader, D, Ayers, A, Harrison, W, North, J, Belagodu, Z, Parasomthy, R, Olufuwa, O, Gherman, A, Fuller, B, Stuart, C, Kelsall, O, Davis, C, Wild, L, Wood, H, Thrush, J, Durie, A, Austin', K, Archer, K, Anderson, P, Vigurs, C, Thorpe, C, Knights, E, Boyle, N, Price, A, Kubisz-Pudelko, A, Wood, D, Lewis, A, Board, S, Pippard, L, Perry, J, Beesley, K, Rattray, A, Lee, E, Lennon, L, Douglas, K, Bell, D, Boyle, R, Glass, L, M Nauman Akhtar, Dent, K, Potoczna, D, Pearson, S, Horsley, E, Spencer, S, Mullan, D, Skinner, D, Gaylard, J, Ortiz-Ruizdegordoa, L, Barber, R, Hewitt, C, Hilldrith, A, Shepardson, S, Wills, M, Jackson-Lawrence, K, Gupta, A, Easthope, A, Timlick, E, Gorman, C, Otaha, I, Gales, A, Coetzee, S, Raj, M, Peiu, M, Quaid, S, Watson, E, Elliott, K, Mallinson, J, Chandler, B, Turnbull, A, Finch, C, Holl, C, Cooper, J, Evans, A, Khaliq, W, Collins, A, E Treus Gude, Love, N, L van Koutrik, Hunt, J, Kaye, D, Fisher, E, Brayne, A, Tuckey, V, Jackson, P, Parkin, J, Raith, E, Tariq, A, Houlden, H, Tucci, A, Hardy, J, Moncur, E, Highgate, J, Cowley, A, Mitra, A, Stead, R, Behan, T, Burnett, C, Newton, M, Heeney, E, Pollard, R, Hatton, J, Patel, A, Kasipandian, V, Allibone, S, M Genetu, R, Otahal, I, O'Brien, L, Omar, Z, Perkins, E, Davies, K, Tetla, D, Shelley, B, Irvine, V, Williams, S, Williams, P, Goodsell, J, Tutton, R, Bough, L, Winter-Goodwin, B, Kitson, R, Pinnell, J, Wilson, A, Nortcliffe, T, Wood, T, Home, M, Holdroyd, K, Robinson, M, Shaw, R, Greig, J, Brady, M, Haigh, A, Matupe, L, Usher, M, Mellor, S, Dale, S, Gledhill, L, Shaw, L, Turner, G, Kelly, D, Anwar, B, Riley, H, Sturgeon, H, Ali, A, Thomis, L, Melia, D, Dance, A, Hanson, K, Humphreys, S, Frost, I, Gopal, V, Godden, J, Holden, A, Swann, S, Smith, T, Clapham, M, Poultney, U, Harper, R, Rice, P, Reece-Anthony, R, Gurung, B, Moultrie, S, Odam, M, Mayer, A, Bellini, A, Pickard, A, Bryant, J, Roe, N, Sowter, J, Lang, K, Taylor, J, Barry, P, Hobrok, M, Tench, H, Wolf-Roberts, R, Mcguinness, H, Loosley, R, Hawcutt, D, Rad, L, O'Malley, L, Saunderson, P, Seddon, G, Anderson, T, Rogers, N, Ruddy, J, Harkins, M, Beith, C, Mcalpine, A, Ferguson, L, Grant, P, Macfadyen, S, Mclaughlin, M, Baird, T, Rundell, S, Welsh, B, Hamill, R, Fisher, F, Gregory, J, Axel, Schmidt, Kerstin, U Ludwig, Selina, Rolker, Markus, M Nöthen, Julia, Fazaal, Verena, Keitel, Björn, Jensen, Torsten, Feldt, Lisa, Knopp, Julia, Schröder, Carlo, Maj, Fabian, Brand, Marc, M Berger, Thorsten, Brenner, Anke, Hinney, Oliver, Witzke, Robert, Bals, Christian, Herr, Nicole, Ludwig, Jörn, Walter, Jochen, Schneider, Johanna, Erber, Christoph, D Spinner, Clemens, M Wendtner, Christof, Winter, Ulrike, Protzer, Nicolas, Casadei, Stephan, Ossowski, Olaf, H Riess, Eva, C Schulte, J Brent Richards, Guillaume, Butler-Laporte, Mirosław, Kwasniewski, Urszula, Korotko, Karolina, Chwialkowska, Magdalena, Niemira, Jerzy, Jaroszewicz, Barbara, Sobala-Szczygiel, Beata, Puzanowska, Anna, Parfieniuk-Kowerda, Diana, Martonik, Anna, Moniuszko-Malinowska, Sławomir, Pancewicz, Dorota, Zarębska-Michaluk, Krzysztof, Simon, Monika, Pazgan-Simon, Iwona, Mozer-Lisewska, Maciej, Bura, Agnieszka, Adamek, Krzysztof Tomasiewicz Małgorzata Pawłowska, Anna, Piekarska, Aleksandra, Berkan-Kawinska, Andrzej, Horban, Justyna, Kowalska, Regina, Podlasin, Piotr, Wasilewski, Arsalin, Azzadin, Miroslaw, Czuczwar, Slawomir, Czaban, Paweł, Olszewski, Jacek, Bogocz, Magdalena, Ochab, Anna, Kruk, Sandra, Uszok, Agnieszka, Bielska, Anna, Szałkowska, Justyna, Raczkowska, Gabriela, Sokołowska, Joanna, Chorostowska-Wynimko, Aleksandra, Jezela-Stanek, Adriana, Roży, Urszula, Lechowicz, Urszula, Polowianiuk, Kamil, Grubczak, Aleksandra, Starosz, Andrzej, Eljaszewicz, Wiktoria, Izdebska, Adam, Krętowski, Robert, Flisiak, Marcin Moniuszko Malak Abedalthagafi Manal Alaamery, Salam, Massadeh, Mohamed, Fawzy, Hadeel, Albardis, Nora, Aljawini, Moneera, Alsuwailm, Faisal, Almalki, Serghei, Mangul, Junghyun, Jung, Hamdi, Mbarek, Chadi, Saad, Yaser, Al-Sarraj, Wadha, Al-Muftah, Radja, Badji, Asma Al Thani, Said, I Ismail, HGI, WES/WGS Working Group Within the, Consortium, GenOMICC, Study, GEN-COVID Multicenter, Renieri, Alessandra [0000-0002-0846-9220], Apollo - University of Cambridge Repository, NIHR, Fallerini, C, Picchiotti, N, Baldassarri, M, Zguro, K, Daga, S, Fava, F, Benetti, E, Amitrano, S, Bruttini, M, Palmieri, M, Croci, S, Lista, M, Beligni, G, Valentino, F, Meloni, I, Tanfoni, M, Minnai, F, Colombo, F, Cabri, E, Fratelli, M, Gabbi, C, Mantovani, S, Frullanti, E, Gori, M, Crawley, F, Butler-Laporte, G, Richards, B, Zeberg, H, Lipcsey, M, Hultström, M, Ludwig, K, Schulte, E, Pairo-Castineira, E, Baillie, J, Schmidt, A, Frithiof, R, Mari, F, Renieri, A, Furini, S, and Crotti, L
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Male ,Medicin och hälsovetenskap ,Linkage disequilibrium ,Medizin ,severity ,Genome-wide association study ,Disease ,WES/WGS Working Group Within the HGI ,Logistic regression ,Severity of Illness Index ,Medical and Health Sciences ,Whole Exome Sequencing ,Cohort Studies ,0302 clinical medicine ,Lasso (statistics) ,GEN-COVID Multicenter Study ,Germany ,80 and over ,Genetics (clinical) ,Exome sequencing ,Original Investigation ,Genetics & Heredity ,Aged, 80 and over ,0303 health sciences ,Adult ,Aged ,COVID-19 ,Female ,Humans ,Italy ,Middle Aged ,Polymorphism, Single Nucleotide ,Quebec ,SARS-CoV-2 ,Sweden ,United Kingdom ,Genetic Predisposition to Disease ,Phenotype ,Single Nucleotide ,covid-19 ,1104 Complementary and Alternative Medicine ,GenOMICC Consortium ,Human ,coding variants ,Computational biology ,Biology ,03 medical and health sciences ,Exome Sequencing ,Genetics ,Polymorphism ,Gene ,030304 developmental biology ,0604 Genetics ,1114 Paediatrics and Reproductive Medicine ,Cohort Studie ,030217 neurology & neurosurgery ,Coding (social sciences) - Abstract
The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. Supplementary Information The online version contains supplementary material available at 10.1007/s00439-021-02397-7.
- Published
- 2021
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