Stratified analyses refine association between TLR7 rare variants and severe COVID-19
Boos, Jannik (University of Bonn School of Medicine and University Hospital Bonn (Alemanya))
van der Made, C.I. (Radboud University Medical Center (Nijmegen, Països Baixos))
Ramakrishnan, G. (Radboud University Medical Center (Nijmegen, Països Baixos))
Coughlan, E. (University of Edinburgh)
Asselta, R. (IRCCS Humanitas Research Hospital - via Manzoni 56)
Löscher, B.S. (Kiel University and University Medical Center)
Valenti, L.V.C. (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Milà, Itàlia))
de Cid, Rafael (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Bujanda, Luis (Instituto de Salud Carlos III)
Julià Cano, Antonio (Vall d'Hebron Institut de Recerca (VHIR))
Pairo-Castineira, E. (University of Edinburgh)
Baillie, J.K.
May, S. (Kiel University and University Medical Center)
Zametica, B. (University of Bonn School of Medicine and University Hospital Bonn)
Heggemann, J. (University of Bonn School of Medicine and University Hospital Bonn)
Albillos, Agustín (Universidad de Alcalá)
Banales, Jesus (Universidad de Navarra)
Barretina, Jordi (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Blay, Natalia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Bonfanti, Paolo (Università degli Studi di Milano Bicocca)
Buti, Maria (Instituto de Salud Carlos III)
Fernandez, J. (European Foundation for the Study of Chronic Liver Failure (EF CLif))
Marsal, Sara (Vall d'Hebron Institut de Recerca (VHIR))
Prati, D. (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Milà, Itàlia))
Ronzoni, L. (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Milà, Itàlia))
Sacchi, N. (IBMDR. E.O. Ospedali Galliera)
Rimoldi, V.
Paraboschi, E.M.
Bandera, A.
Peyvandi, Flora
Grasselli, G.
Blasi, Francesco
Malvestiti, F.
Pelusi, S.
Bianco, C.
Miano, L.
Lombardi, A.
Invernizzi, P.
Gerussi, A.
Citerio, Giuseppe
Biondi, A.
Valsecchi, M.G.
Cazzaniga, M.E.
Foti, Giuseppe
Beretta, I.
D'Angiò, M.
Bettini, L.R.
Farré Ramon, Xavier
Iraola-Guzmán, S.
Kogevinas, Manolis
Castaño-Vinyals, Gemma
Garcia-Etxebarria, K.
Nafria, B.
D'Amato, M.
Palom, Adriana
Begg, C.
Clohisey, S.
Hinds, C.
Horby, P.
Knight, J.
Ling, L.
Maslove, D.
McAuley, D.
Millar, J.
Montgomery, Hugh
Nichol, A.
Openshaw, P.J.M.
Pereira, A.C.
Ponting, C.P.
Rowan, K.
McFarland, D.
Cosgrove, D.
Ahmed, A.
Morris, A.
Jakkula, S.
Ali, A.
Brady, M.
Semple, M.G.
Dale, S.
Dance, A.
Gledhill, L.
Greig, J.
Hanson, K.
Holdroyd, K.
Home, M.
Kelly, D.
Kitson, R.
Matapure, L.
Shankar-Hari, M.
Melia, D.
Mellor, S.
Nortcliffe, T.
Pinnell, J.
Robinson, M.
Shaw, L.
Shaw, R.
Thomis, L.
Wilson, A.
Wood, T.
Summers, Charlotte
Bayo, L.A.
Merwaha, E.
Ishaq, T.
Hanley, S.
Hibbert, M.
Tetla, D.
Woodford, C.
Durga, L.
Kennard-Holden, G.
Branney, D.
Walsh, T.
Frankham, J.
Pitts, S.
White, N.
Laha, S.
Verlander, M.
Williams, A.
Altabaibeh, A.
Alvaro, A.
Gilbert, K.
Ma, L.
Aravindan, L.
Mostoles, L.
Parmar, C.
Simpson, K.
Jetha, C.
Booker, L.
Pratley, A.
Adams, C.
Agasou, A.
Arden, T.
Bowes, A.
Armstrong, R.
Boyle, P.
Beekes, M.
Button, H.
Capps, N.
Carnahan, M.
Carter, A.
Childs, D.
Donaldson, D.
Hard, K.
Hurford, F.
Biggs, H.
Hussain, Y.
Javaid, A.
Jones, J.
Jose, S.
Leigh, M.
Martin, T.
Millward, H.
Motherwell, N.
Rikunenko, R.
Stickley, J.
Boz, C.
Summers, J.
Ting, L.
Tivenan, H.
Tonks, L.
Wilcox, R.
Holland, M.
Keenan, N.
Lyons, M.
Wassall, H.
Marsh, C.
Brown, A.
Mahenthran, M.
Carter, E.
Kong, T.
Blackman, H.
Creagh-Brown, B.
Donlon, S.
Michalak-Glinska, N.
Mtuwa, S.
Pristopan, V.
Salberg, A.
Clark, R.
Smith, E.
Stone, S.
Piercy, C.
Verula, J.
Burda, D.
Montaser, R.
Harden, L.
Mayangao, I.
Marriott, C.
Bradley, P.
Coutts, A.
Harris, C.
Anderson, S.
Andrews, E.
Birch, J.
Collins, E.
Hammerton, K.
O'Leary, R.
Clark, M.
Purvis, S.
Barber, R.
Coyle, J.
Hewitt, C.
Hilldrith, A.
Jackson-Lawrence, K.
Shepardson, S.
Wills, M.
Butler, S.
Tavares, S.
Cunningham, A.
Hindale, J.
Arif, S.
Cullum, L.
Bean, S.
Burt, K.
Spivey, M.
Demetriou, C.
Eckbad, C.
Hierons, S.
Howie, L.
Mitchard, S.
Ramos López, Laura
Serrano-Ruiz, A.
Das, S.
White, K.
Kelly, F.
Cristiano, D.
Dormand, N.
Farzad, Z.
Gummadi, M.
Liyanage, K.
Patel, B.
Salmi, S.
Sloane, G.
Day, N.
Thwaites, V.
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Zborowski, A.C.
Allan, J.
Geary, T.
Houston, G.
Meikle, A.
O'Brien, P.
Forsey, M.
Kaliappan, A.
Donnelly, L.
Nicholson, A.
Riches, J.
Vertue, M.
Allan, E.
Darlington, K.
Davies, F.
Easton, Jack
Kumar, S.
Lean, R.
Menzies, D.
Duncan, E.
Pugh, R.
Qiu, X.
Davies, L.
Williams, H.
Scanlon, J.
Davies, G.
Mackay, C.
Lewis, J.
Rees, S.
Oblak, M.
Fawkes, A.
Popescu, M.
Thankachen, M.
Higham, A.
Craig, J.
Baruah, R.
Morris, S.
Ferguson, S.
Shepherd, A.
Prockter Moore, L.S.
Fineran, P.
Vizcaychipi, M.P.
Gomes de Almeida Martins, L.
Carungcong, J.
Mohamed Ali, I.A.
Beaumont, K.
Blunt, M.
Coton, Z.
Curgenven, H.
Elsaadany, M.
Fernandes, K.
Fourman, M.H.
Ally, S.M.
Rangarajan, H.
Sarathy, V.
Selvanayagam, S.
Vedage, D.
White, M.
Gill, M.
Paul, P.
Ratnam, V.
Shelton, S.
Furlong, A.
Wynter, I.
Carmody, S.
Page, V.J.
Beith, C.M.
Black, K.
Clements, S.
Morrison, A.
Strachan, D.
Taylor, M.
Clarkson, M.
Furniss, J.
D'Sylva, S.
Norman, K.
Auld, F.
Donnachie, J.
Edmond, I.
Prentice, L.
Runciman, N.
Salutous, D.
Symon, L.
Todd, A.
Gallagher, B.
Turner, P.
Short, A.
Sweeney, L.
Murdoch, E.
Senaratne, D.
Hill, M.
Kannan, T.
Laura, W.
Crawley, R.
Crew, A.
Gilchrist, T.
Cunningham, M.
Daniels, A.
Harrison, L.
Hope, S.
Inweregbu, K.
Jones, S.
Lancaster, N.
Matthews, J.
Wray, G.
Golightly, A.
Langton, H.
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Collins, C.
Kaul, S.
Passmore, H.
Prendergast, C.
Reed, A.
Griffiths, F.
Rogers, P.
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Polgar, O.
Nolan, C.
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Hamilton, D.
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Latif, M.
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Glass, L.
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Hughes, R.A.
Thomas, H.
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Quaid, S.
Watson, E.
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Brayne, A.
Fisher, E.
Hunt, J.
Jackson, P.
Kaye, D.
Love, N.
Parkin, J.
Tuckey, V.
Van Koutrik, L.
Carter, S.
Turtle, L.
Andrew, B.
Findlay, L.
Adams, Katie
Service, J.
Cheyne, C.
Saunderson, A.
Moultrie, S.
Odam, M.
Hall, K.
Wackett, T.
Mapfunde, I.
Willis, C.
Lyon, A.
Sri-Chandana, C.
Scherewode, J.
Stephenson, L.
Marsh, S.
Hardy, J.
Houlden, Henry
Moncur, E.
Ward, M.
Tariq, Akash
Tucci, A.
Hobrok, M.
Loosley, R.
McGuinness, H.
Tench, H.
Wolf-Roberts, R.
Irvine, V.
Shelley, B.
Gorman, C.
Weaver, J.
Gupta, Arunava
Timlick, E.
Brady, R.
Milligan, B.
Bellini, A.
Bryant, J.
Mayer, A.
Pickard, A.
Roe, N.
Sowter, J.
Wrobel, N.
Howlett, A.
Fidler, K.
Tagliavini, E.
Donnelly, K.
Schultze, J.L. (University of Bonn)
Riess, O. (University of Tübingen)
Franke, Andre (Kiel University and University Medical Center)
Rawlik, Konrad (University of Edinburgh)
Ellinghaus, D. (Kiel University and University Medical Center)
Hoischen, A. (Radboud University Medical Center)
Zechner, M.
Schmidt, Axel (University of Bonn School of Medicine and University Hospital Bonn)
Ludwig, Kerstin U. (University of Bonn School of Medicine and University Hospital Bonn)
Universitat Autònoma de Barcelona

Data:	2024
Resum:	Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2. 4% of young (<60 years) cases with no reported clinical risk factors (n = 378), compared to 0. 24% of controls (odds ratio [OR] = 12. 3, p = 1. 27 × 10). Incorporation of the results of either functional assays or protein modeling led to a pronounced increase in effect size (OR = 46. 5, p = 1. 74 × 10). Association signals for the X-chromosomal gene TLR7 were also detected in the female-only subgroup, suggesting the existence of additional mechanisms beyond X-linked recessive inheritance in males. Additionally, supporting evidence was generated for a contribution to severe COVID-19 of the previously implicated genes IFNAR2, IFIH1, and TBK1. Our results refine the genetic contribution of rare TLR7 variants to severe COVID-19 and strengthen evidence for the etiological relevance of genes in the interferon signaling pathway.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	SARS-CoV-2 ; Burden analysis ; Host genetics ; Immune deficiency ; Infection ; Innate immunity ; Rare variants ; Targeted sequencing ; Toll-like receptor 7 ; Variant collapsing analysis
Publicat a:	Human Genetics and Genomics Advances, Vol. 5 Núm. 4 (october 2024) , p. 100323, ISSN 2666-2477

DOI: 10.1016/j.xhgg.2024.100323
PMID: 38944683

12 p, 3.2 MB

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