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Detailed stratified GWAS analysis for severe COVID-19 in four European populations

Permanent link
https://hdl.handle.net/10037/26836
DOI
https://doi.org/10.1093/hmg/ddac158
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Accepted manuscript version (PDF)
Date
2022-07-15
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Author
Ellinghaus, David; Degenhardt, Frauke; Juzenas, Simonas; Lerga-Jaso, Jon; Wendorff, Mareike; Maya-Miles, Douglas; Uellendahl-Werth, Florian; ElAbd, Hesham; Lenning, Ole Bernt; Myhre, Ronny; Vadla, May Sissel; Holten, Aleksander Rygh; Kildal, Anders Benjamin; Lind, Andreas; Dyrhol-Riise, Anne Ma; Hoff, Dag Arne Lihaug; Müller, Fredrik; Solligård, Erik; Holter, Jan Cato; Afset, Jan Egil; Damås, Jan Kristian; Bergan, Jonas; Risnes, Kari; Muller, Karl Erik; Tonby, Kristian; Heggelund, Lars; Tuset Gustad, Trine; Grimsrud, Marit Mæhle; Dudman, Susanne Gjeruldsen; Folseraas, Trine; Skogen, Vegard; Hov, Johannes Espolin Roksund; Karlsen, Tom Hemming
Abstract
Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen (HLA) region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ~ 0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5threlease of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian individuals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.
Publisher
Oxford University Press
Citation
Ellinghaus D, Degenhardt F, Juzenas S, Lerga-Jaso, Wendorff M, Maya-Miles D, Uellendahl-Werth F, ElAbd H, Lenning OB, Myhre R, Vadla MS, Holten AR, Kildal AB, Lind AL, Dyrhol-Riise AM, Hoff DA, Müller F, Solligård E, Holter JC, Afset JE, Damås JK, Bergan J, Risnes K, Muller KE, Tonby K, Heggelund L, Tuset Gustad, Grimsrud MM, Dudman SG, Folseraas T, Skogen V, Hov JR, Karlsen HT. Detailed stratified GWAS analysis for severe COVID-19 in four European populations. Human Molecular Genetics. 2022
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