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 in...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-12-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012786 |
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| author | Axel Schmidt Nicolas Casadei Fabian Brand German Demidov Elaheh Vojgani Ayda Abolhassani Rana Aldisi Guillaume Butler-Laporte DeCOI host genetics group T Madhusankha Alawathurage Max Augustin Robert Bals Carla Bellinghausen Marc Moritz Berger Michael Bitzer Christian Bode Jannik Boos Thorsten Brenner Oliver A Cornely Thomas Eggermann Johanna Erber Torsten Feldt Christian Fuchsberger Julien Gagneur Siri Göpel Tobias Haack Helene Häberle Frank Hanses Julia Heggemann Ute Hehr Johannes C Hellmuth Christian Herr Anke Hinney Per Hoffmann Thomas Illig Björn-Erik Ole Jensen Verena Keitel Sarah Kim-Hellmuth Philipp Koehler Ingo Kurth Anna-Lisa Lanz Eicke Latz Clara Lehmann Tom Luedde Carlo Maj Michael Mian Abigail Miller Maximilian Muenchhoff Isabell Pink Ulrike Protzer Hana Rohn Jan Rybniker Federica Scaggiante Anna Schaffeldt Clemens Scherer Maximilian Schieck Susanne V Schmidt Philipp Schommers Christoph D Spinner Maria J G T Vehreschild Thirumalaisamy P Velavan Sonja Volland Sibylle Wilfling Christof Winter J Brent Richards DeCOI André Heimbach Kerstin Becker Stephan Ossowski Joachim L Schultze Peter Nürnberg Markus M Nöthen Susanne Motameny Michael Nothnagel Olaf Riess Eva C Schulte Kerstin U Ludwig |
| author_facet | Axel Schmidt Nicolas Casadei Fabian Brand German Demidov Elaheh Vojgani Ayda Abolhassani Rana Aldisi Guillaume Butler-Laporte DeCOI host genetics group T Madhusankha Alawathurage Max Augustin Robert Bals Carla Bellinghausen Marc Moritz Berger Michael Bitzer Christian Bode Jannik Boos Thorsten Brenner Oliver A Cornely Thomas Eggermann Johanna Erber Torsten Feldt Christian Fuchsberger Julien Gagneur Siri Göpel Tobias Haack Helene Häberle Frank Hanses Julia Heggemann Ute Hehr Johannes C Hellmuth Christian Herr Anke Hinney Per Hoffmann Thomas Illig Björn-Erik Ole Jensen Verena Keitel Sarah Kim-Hellmuth Philipp Koehler Ingo Kurth Anna-Lisa Lanz Eicke Latz Clara Lehmann Tom Luedde Carlo Maj Michael Mian Abigail Miller Maximilian Muenchhoff Isabell Pink Ulrike Protzer Hana Rohn Jan Rybniker Federica Scaggiante Anna Schaffeldt Clemens Scherer Maximilian Schieck Susanne V Schmidt Philipp Schommers Christoph D Spinner Maria J G T Vehreschild Thirumalaisamy P Velavan Sonja Volland Sibylle Wilfling Christof Winter J Brent Richards DeCOI André Heimbach Kerstin Becker Stephan Ossowski Joachim L Schultze Peter Nürnberg Markus M Nöthen Susanne Motameny Michael Nothnagel Olaf Riess Eva C Schulte Kerstin U Ludwig |
| author_sort | Axel Schmidt |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1e791f568ea0417a9070a1420ba5cbc7 |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-1e791f568ea0417a9070a1420ba5cbc72025-01-17T05:31:03ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742024-12-012012e101278610.1371/journal.ppat.1012786Systematic assessment of COVID-19 host genetics using whole genome sequencing data.Axel SchmidtNicolas CasadeiFabian BrandGerman DemidovElaheh VojganiAyda AbolhassaniRana AldisiGuillaume Butler-LaporteDeCOI host genetics groupT Madhusankha AlawathurageMax AugustinRobert BalsCarla BellinghausenMarc Moritz BergerMichael BitzerChristian BodeJannik BoosThorsten BrennerOliver A CornelyThomas EggermannJohanna ErberTorsten FeldtChristian FuchsbergerJulien GagneurSiri GöpelTobias HaackHelene HäberleFrank HansesJulia HeggemannUte HehrJohannes C HellmuthChristian HerrAnke HinneyPer HoffmannThomas IlligBjörn-Erik Ole JensenVerena KeitelSarah Kim-HellmuthPhilipp KoehlerIngo KurthAnna-Lisa LanzEicke LatzClara LehmannTom LueddeCarlo MajMichael MianAbigail MillerMaximilian MuenchhoffIsabell PinkUlrike ProtzerHana RohnJan RybnikerFederica ScaggianteAnna SchaffeldtClemens SchererMaximilian SchieckSusanne V SchmidtPhilipp SchommersChristoph D SpinnerMaria J G T VehreschildThirumalaisamy P VelavanSonja VollandSibylle WilflingChristof WinterJ Brent RichardsDeCOIAndré HeimbachKerstin BeckerStephan OssowskiJoachim L SchultzePeter NürnbergMarkus M NöthenSusanne MotamenyMichael NothnagelOlaf RiessEva C SchulteKerstin U LudwigCourses 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.https://doi.org/10.1371/journal.ppat.1012786 |
| spellingShingle | Axel Schmidt Nicolas Casadei Fabian Brand German Demidov Elaheh Vojgani Ayda Abolhassani Rana Aldisi Guillaume Butler-Laporte DeCOI host genetics group T Madhusankha Alawathurage Max Augustin Robert Bals Carla Bellinghausen Marc Moritz Berger Michael Bitzer Christian Bode Jannik Boos Thorsten Brenner Oliver A Cornely Thomas Eggermann Johanna Erber Torsten Feldt Christian Fuchsberger Julien Gagneur Siri Göpel Tobias Haack Helene Häberle Frank Hanses Julia Heggemann Ute Hehr Johannes C Hellmuth Christian Herr Anke Hinney Per Hoffmann Thomas Illig Björn-Erik Ole Jensen Verena Keitel Sarah Kim-Hellmuth Philipp Koehler Ingo Kurth Anna-Lisa Lanz Eicke Latz Clara Lehmann Tom Luedde Carlo Maj Michael Mian Abigail Miller Maximilian Muenchhoff Isabell Pink Ulrike Protzer Hana Rohn Jan Rybniker Federica Scaggiante Anna Schaffeldt Clemens Scherer Maximilian Schieck Susanne V Schmidt Philipp Schommers Christoph D Spinner Maria J G T Vehreschild Thirumalaisamy P Velavan Sonja Volland Sibylle Wilfling Christof Winter J Brent Richards DeCOI André Heimbach Kerstin Becker Stephan Ossowski Joachim L Schultze Peter Nürnberg Markus M Nöthen Susanne Motameny Michael Nothnagel Olaf Riess Eva C Schulte Kerstin U Ludwig Systematic assessment of COVID-19 host genetics using whole genome sequencing data. PLoS Pathogens |
| title | Systematic assessment of COVID-19 host genetics using whole genome sequencing data. |
| title_full | Systematic assessment of COVID-19 host genetics using whole genome sequencing data. |
| title_fullStr | Systematic assessment of COVID-19 host genetics using whole genome sequencing data. |
| title_full_unstemmed | Systematic assessment of COVID-19 host genetics using whole genome sequencing data. |
| title_short | Systematic assessment of COVID-19 host genetics using whole genome sequencing data. |
| title_sort | systematic assessment of covid 19 host genetics using whole genome sequencing data |
| url | https://doi.org/10.1371/journal.ppat.1012786 |
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