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

• DOI: 10.1371/journal.ppat.1012786
• Publication Date: 2024-12-23T18:47:31Z
• Authors: Axel Schmidt; Nicolas Casadei; Fabian Brand; German Demidov; Elaheh Vojgani; Ayda Abolhassani; Rana Aldisi; Guillaume Butler-...; ; T. Madhusankha Al...; 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 Fuchsbe...; 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 Je...; 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 Muench...; 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. Ve...; Thirumalaisamy P....; Sonja Volland; Sibylle Wilfling; Christof Winter; J. Brent Richards; ; 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
• Keywords: Genome-wide Association Study

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 this variability, cohort-based joint analyses variants the entire allelic spectrum in individuals with confirmed still lacking. Here, we present results whole genome sequencing 1,220 mainly vaccine-naïve infection, including 827 hospitalized COVID-19 cases. We observed presence autosomal-recessive or likely compound heterozygous monogenic disorders six individuals, all which were and significantly younger than rest cohort. did not observe any suggestive causal around established risk gene TLR7 . Burden testing largest population subgroup (i.e., Europeans) suggested nominal enrichments rare coding non-coding regions interferon immune response genes overall analysis male subgroup. Case-control more common associations previously reported loci, key locus at 3p21 reaching genome-wide significance. Polygenic scores accurately captured an age-dependent manner. By enabling different types variation across frequency spectrum, data will continue elucidation etiology.