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

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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Journal
PLoS Pathogens
Published
2024-12-23
DOI
https://doi.org/10.1371/journal.ppat.1012786
Citations
1
Primary Topic
interferon and immune responses
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article
Field-Weighted Citation Impact
0.24

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article

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

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1 citations
PLoS Pathogens
interferon and immune responses
0.24
article

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

Julien Gagneur, Tom Luedde, Michael Bitzer, Anke Hinney, Sibylle Wilfling, Michael Nothnagel, Eicke Latz, Johanna Erber, Anna-Lisa Lanz, Tobias B. Haack, Clemens Scherer, Susanne V. Schmidt, Philipp Schommers, Ingo Kurth, Hana Rohn, Thomas Eggermann, Siri Goepel, Federica Scaggiante, André Heimbach, Christian Bode, Frank Hanses, Per Hoffmann, Axel Schmidt, Thorsten Brenner, Carlo Maj, Christian Fuchsberger, J. Brent Richards, Ayda Abolhassani, Kerstin Becker, Elaheh Vojgani, Sarah Kim-Hellmuth, Julia Heggemann, Jörg Janne Vehreschild, Christoph D. Spinner, Jan Rybniker, Nicolas Casadei, Eva Christina Schulte, Björn‐Erik Ole Jensen, Rana Aldisi, Robert Bals, Fabian Brand, Max Augustin, Philipp Koehler, Michael Mian, Clara Lehmann, Olaf Rieß, Sonja Volland, Johannes C. Hellmuth, Thirumalaisamy P. Velavan, Marc Moritz Berger, Susanne Motameny, Christian Herr, Isabell Pink, Carla Bellinghausen, Oliver A. Cornely, Thomas Illig, Kerstin U. Ludwig, Joachim L. Schultze, Maximilian Muenchhoff, Peter Nürnberg, Jannik Boos, Verena Keitel, Maximilian Schieck, Christof Winter, Stephan Ossowski, Guillaume Butler‐Laporte, Ute Hehr, Torsten Feldt, Markus M. Nöthen, Ulrike Protzer, German Demidov, Helene Häberle, Abigail Miller, Anna Schaffeldt, T. Madhusankha Alawathurage
article en
1 citations

Abstract

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.

PLoS PathogensVol. 20(12)
Goethe University Frankfurt (DE), Eurac Research (IT), Centre for Human Genetics (GB), University of Bonn (DE), German Sport University Cologne (DE), Philipps University of Marburg (DE), German Cancer Research Center (DE), University of Cologne (DE), King's College London (GB), Heidelberg University (DE), Paracelsus Medical University (AT), University Hospital Bonn (DE), German Center for Neurodegenerative Diseases (DE), McGill University Health Centre (CA), Jewish General Hospital (CA), TUM Klinikum (DE), Helmholtz Zentrum München (DE), LMU Klinikum (DE), University Hospital Regensburg (DE), Medizinische Hochschule Hannover (DE), University of Oxford (GB), Düsseldorf University Hospital (DE), Ospedale di Bolzano (IT), Universitätsklinikum Tübingen (DE), German Center for Infection Research (DE), Institute for Biomedicine (IT), University Children's Hospital Tübingen (DE), Krankenhaus Brixen (IT), University Hospital Frankfurt (DE), Bernstein Center for Computational Neuroscience Tübingen (DE), Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE), Helmholtz Institute for Pharmaceutical Research Saarland (DE), Vietnamese - German Center of Excellence in Medical Research (VN), University Hospital Cologne (DE), Deutsches Konsortium für Translationale Krebsforschung (DE), Heinrich Heine University Düsseldorf (DE), McGill University (CA), University of Regensburg (DE), University of Duisburg-Essen (DE), Technical University of Munich (DE), University of Tübingen (DE), Ludwig-Maximilians-Universität München (DE), RWTH Aachen University (DE), Saarland University (DE)
Care-for-Rare Foundation, Illumina, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Technische Universität München, RWTH Aachen University, Rheinische Friedrich-Wilhelms-Universität Bonn, Stiftung Universitätsmedizin Essen, Provincia autonoma di Bolzano - Alto Adige, College of Medicine Office of Research, Ohio State University, Heidelberger Zentrum für Personalisierte Onkologie Deutsches Krebsforschungszentrum In Der Helmholtz-Gemeinschaft, European Research Council, Medizinische Fakultät, Rheinische Friedrich-Wilhelms-Universität Bonn
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interferon and immune responses
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