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

A Schmidt; N Casadei; F Brand; G Demidov; E Vojgani; A Abolhassani; R Aldisi; G Butler-Laporte; group DeCOI host genetics; TM Alawathurage; M Augustin; R Bals; C Bellinghausen; MM Berger; M Bitzer; C Bode; J Boos; T Brenner; OA Cornely; T Eggermann; J Erber; T Feldt; Christian Fuchsberger; J Gagneur; S Göpel; T Haack; H Häberle; F Hanses; J Heggemann; U Hehr; JC Hellmuth; C Herr; A Hinney; P Hoffmann; T Illig; BO Jensen; V Keitel; S Kim-Hellmuth; P Koehler; I Kurth; AL Lanz; E Latz; C Lehmann; T Luedde; C Maj; M Mian; A Miller; M Muenchhoff; I Pink; U Protzer; H Rohn; J Rybniker; F Scaggiante; A Schaffeldt; C Scherer; M Schieck; SV Schmidt; P Schommers; CD Spinner; MJGT Vehreschild; TP Velavan; S Volland; S Wilfling; C Winter; JB Richards; A Heimbach; K Becker; S Ossowski; JL Schultze; P Nürnberg; MM Nöthen; S Motameny; M Nothnagel; O Riess; EC Schulte; KU Ludwig

doi:10.1371/journal.ppat.1012786

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

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

A Schmidt, N Casadei, F Brand, G Demidov, E Vojgani, A Abolhassani, R Aldisi, G Butler-Laporte, group DeCOI host genetics, TM Alawathurage, …

PLoS Pathogens, Vol.20(12)

23/12/2024

DOI: https://doi.org/10.1371/journal.ppat.1012786

Handle:

https://hdl.handle.net/10863/48878

PMID: 39715278

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.

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Title: Systematic assessment of COVID-19 host genetics using whole genome sequencing data
Creators: A Schmidt - University Hospital Bonn
N Casadei - University of Tübingen
F Brand - University Hospital Bonn
G Demidov - University of Tübingen
E Vojgani - University of Cologne
A Abolhassani - University Hospital Bonn
R Aldisi - University Hospital Bonn
G Butler-Laporte - University of Oxford
group DeCOI host genetics
TM Alawathurage - University Hospital Bonn
M Augustin - University Hospital Cologne
R Bals - Helmholtz Institute for Pharmaceutical Research Saarland
C Bellinghausen - University Hospital Frankfurt
MM Berger - University of Duisburg-Essen
M Bitzer - University Children's Hospital Tübingen
C Bode - University Hospital Bonn
J Boos - University Hospital Bonn
T Brenner - University of Duisburg-Essen
OA Cornely - Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
T Eggermann - RWTH Aachen University
J Erber - Klinikum rechts der Isar
T Feldt - Heinrich Heine University Düsseldorf
Christian Fuchsberger - Eurac Research
J Gagneur - Technical University of Munich
S Göpel
T Haack - University of Tübingen
H Häberle - University Children's Hospital Tübingen
F Hanses - University Hospital Regensburg
J Heggemann - University Hospital Bonn
U Hehr
JC Hellmuth - Ludwig-Maximilians-Universität München
C Herr - Saarland University
A Hinney - University of Duisburg-Essen
P Hoffmann - University Hospital Bonn
T Illig - Medizinische Hochschule Hannover
BO Jensen - Düsseldorf University Hospital
V Keitel - Heinrich Heine University Düsseldorf
S Kim-Hellmuth - Helmholtz Zentrum München
P Koehler - University of Cologne
I Kurth - RWTH Aachen University
AL Lanz - Ludwig-Maximilians-Universität München
E Latz - University Hospital Bonn
C Lehmann - University Hospital Cologne
T Luedde - Düsseldorf University Hospital
C Maj - Philipps University of Marburg
M Mian - Paracelsus Medical University
A Miller - University Hospital Bonn
M Muenchhoff - Ludwig-Maximilians-Universität München
I Pink - Medizinische Hochschule Hannover
U Protzer - German Center for Infection Research
H Rohn
J Rybniker - University of Cologne
F Scaggiante - Krankenhaus Brixen
A Schaffeldt - RWTH Aachen University
C Scherer - LMU Klinikum
M Schieck - Medizinische Hochschule Hannover
SV Schmidt - University Hospital Bonn
P Schommers - University of Cologne
CD Spinner - Klinikum rechts der Isar
MJGT Vehreschild
TP Velavan - Vietnamese - German Center of Excellence in Medical Research
S Volland - Medizinische Hochschule Hannover
S Wilfling - University Hospital Regensburg
C Winter - Deutschen Konsortium für Translationale Krebsforschung
JB Richards - Jewish General Hospital
A Heimbach - University Hospital Bonn
K Becker - University of Cologne
S Ossowski - University of Tübingen
JL Schultze - German Center for Neurodegenerative Diseases
P Nürnberg - University of Cologne
MM Nöthen - University Hospital Bonn
S Motameny - University of Cologne
M Nothnagel - University of Cologne
O Riess
EC Schulte - University Hospital Bonn
KU Ludwig - University Hospital Bonn
Publication Details: PLoS Pathogens, Vol.20(12)
ISSN: 1553-7366
EISSN: 1553-7374
Series / Volume: 20
Publisher: Public Library of Science
Identifiers: (EURAC)30367604
991007089960501241
Web of Science ID: WOS:001389172500001
Copyright: CC BY 4.0
Academic Unit: Institute for Biomedicine
Language: English
Resource Type: Journal article
Description coverage: none
Description audience: Scientific
Local Fields: Scientific
Author Names String: Schmidt A, Casadei N, Brand F, Demidov G, Vojgani E, Abolhassani A, Aldisi R, Butler-Laporte G, DeCOI host genetics group, Alawathurage TM, Augustin M, Bals R, Bellinghausen C, Berger MM, Bitzer M, Bode C, Boos J, Brenner T, Cornely OA, Eggermann T, Erber J, Feldt T, Fuchsberger C, Gagneur J, Göpel S, Haack T, Häberle H, Hanses F, Heggemann J, Hehr U, Hellmuth JC, Herr C, Hinney A, Hoffmann P, Illig T, Jensen BO, Keitel V, Kim-Hellmuth S, Koehler P, Kurth I, Lanz AL, 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 SV, Schommers P, Spinner CD, Vehreschild MJGT, Velavan TP, Volland S, Wilfling S, Winter C, Richards JB, DeCOI, Heimbach A, Becker K, Ossowski S, Schultze JL, Nürnberg P, Nöthen MM, Motameny S, Nothnagel M, Riess O, Schulte EC, Ludwig KU

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