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Schmidt, A.* ; Casadei, N.* ; Brand, F.* ; Demidov, G.* ; Vojgani, E.* ; Abolhassani, A.* ; Aldisi, R.* ; Butler-Laporte, G.* ; Alawathurage, T.M.* ; Augustin, M.* ; Bals, R.* ; Bellinghausen, C.* ; Berger, M.M.* ; Bitzer, M.* ; Bode, C.* ; Boos, J.* ; Brenner, T.* ; Cornely, O.A.* ; Eggermann, T.* ; Erber, J.* ; Feldt, T.* ; Fuchsberger, C.* ; Gagneur, J. ; Göpel, S.* ; Haack, T.* ; Häberle, H.* ; Hanses, F.* ; Heggemann, J.* ; Hehr, U.* ; Hellmuth, J.C.* ; Herr, C.* ; Hinney, A.* ; Hoffmann, P.* ; Illig, T.* ; Jensen, B.O.* ; Keitel, V.* ; Kim-Hellmuth, S. ; Koehler, P.* ; Kurth, I.* ; Lanz, A.L.* ; Latz, E.* ; Lehmann, C.* ; Luedde, T.* ; Maj, C.* ; Mian, M.* ; Miller, A.* ; Muenchhoff, M.* ; Pink, I.* ; Protzer, U. ; Rohn, H.* ; Rybniker, J.* ; Scaggiante, F.* ; Schaffeldt, A.* ; Scherer, C.* ; Schieck, M.* ; Schmidt, S.V.* ; Schommers, P.* ; Spinner, C.D.* ; Vehreschild, M.J.G.T.* ; Velavan, T.P.* ; Volland, S.* ; Wilfling, S.* ; Winter, C.* ; Richards, J.B.* ; Heimbach, A.* ; Becker, K.* ; Ossowski, S.* ; Schultze, J.L.* ; Nürnberg, P.* ; Nöthen, M.M.* ; Motameny, S.* ; Nothnagel, M.* ; Riess, O.* ; Schulte, E.C. ; Ludwig, K.U.*

Systematic assessment of COVID-19 host genetics using whole genome sequencing data.

PLoS Pathog. 20:e1012786 (2024)
Publ. Version/Full Text DOI PMC
Free journal
Creative Commons Lizenzvertrag
Courses of SARS-CoV-2 infections are highly variable, ranging from asymptomatic to lethal COVID-19. Though research has shown that host genetic factors contribute to this variability, cohort-based joint analyses of variants from the entire allelic spectrum in individuals with confirmed SARS-CoV-2 infections are still lacking. Here, we present the results of whole genome sequencing in 1,220 mainly vaccine-naïve individuals with confirmed SARS-CoV-2 infection, including 827 hospitalized COVID-19 cases. We observed the presence of autosomal-recessive or likely compound heterozygous monogenic disorders in six individuals, all of which were hospitalized and significantly younger than the rest of the cohort. We did not observe any suggestive causal variants in or around the established risk gene TLR7. Burden testing in the largest population subgroup (i.e., Europeans) suggested nominal enrichments of rare variants in coding and non-coding regions of interferon immune response genes in the overall analysis and male subgroup. Case-control analyses of more common variants confirmed associations with previously reported risk loci, with the key locus at 3p21 reaching genome-wide significance. Polygenic scores accurately captured risk in an age-dependent manner. By enabling joint analyses of different types of variation across the entire frequency spectrum, this data will continue to contribute to the elucidation of COVID-19 etiology.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Autoantibodies
ISSN (print) / ISBN 1553-7366
e-ISSN 1553-7374
Journal PLoS Pathogens
Quellenangaben Volume: 20, Issue: 12, Pages: , Article Number: e1012786 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place 1160 Battery Street, Ste 100, San Francisco, Ca 94111 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)
Institute of Computational Biology (ICB)
Institute of Translational Genomics (ITG)
Grants Technical University of Munich
Institute of Human Genetics, University Hospital Bonn
Federal Ministry of Education and Research
Rolf M. Schweite Stiftung
State of Saarland
Uniklinik RWTH Aachen
Institute for Human Genetics and Genomic Medicine at the University Hospital Aachen
UME
Hessisches Ministerium fur Wissenschaft und Kunst
Healthcare System of the Autonomous Province of Bolzano/Bozen
University Hospital Dusseldorf
Ministry of Science and Culture (MWK) of Lower-Saxony
Free State of Bavaria under the Excellence Strategy of the Federal State Government (LMUExcellent)
Care-for-Rare Foundation
BMBF
State of North Rhine-Westphalia
German National Pandemic Cohort Network (Nationales Pandemie Kohorten Netz NAPKON) of the Network University Medicine (Netzwerk-Universitatsmedizin -NUM)
B-FAST (Bundesweites Forschungsnetz Angewandte Surveillance und Testung)
German Research Foundation (Deutsche Forschungsgemeinschaft DFG)
Illumina, Berlin
BONFOR program of the Medical Faculty of the University of Bonn
DFG
ERC Starting Grant
Stiftung Universitatsmedizin Essen
Munich Clinician Scientist Program (MCSP)
German Federal Ministry of Research and Education (BMBF)
Bavarian State Ministry for Science and Art