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

© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissionsoup.com..

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 genome-wide association 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 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 5th release 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.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:31

Enthalten in:

Human molecular genetics - 31(2022), 23 vom: 28. Nov., Seite 3945-3966

Sprache:

Englisch

Beteiligte Personen:

Degenhardt, Frauke [VerfasserIn]
Ellinghaus, David [VerfasserIn]
Juzenas, Simonas [VerfasserIn]
Lerga-Jaso, Jon [VerfasserIn]
Wendorff, Mareike [VerfasserIn]
Maya-Miles, Douglas [VerfasserIn]
Uellendahl-Werth, Florian [VerfasserIn]
ElAbd, Hesham [VerfasserIn]
Rühlemann, Malte C [VerfasserIn]
Arora, Jatin [VerfasserIn]
Özer, Onur [VerfasserIn]
Lenning, Ole Bernt [VerfasserIn]
Myhre, Ronny [VerfasserIn]
Vadla, May Sissel [VerfasserIn]
Wacker, Eike M [VerfasserIn]
Wienbrandt, Lars [VerfasserIn]
Blandino Ortiz, Aaron [VerfasserIn]
de Salazar, Adolfo [VerfasserIn]
Garrido Chercoles, Adolfo [VerfasserIn]
Palom, Adriana [VerfasserIn]
Ruiz, Agustín [VerfasserIn]
Garcia-Fernandez, Alba-Estela [VerfasserIn]
Blanco-Grau, Albert [VerfasserIn]
Mantovani, Alberto [VerfasserIn]
Zanella, Alberto [VerfasserIn]
Holten, Aleksander Rygh [VerfasserIn]
Mayer, Alena [VerfasserIn]
Bandera, Alessandra [VerfasserIn]
Cherubini, Alessandro [VerfasserIn]
Protti, Alessandro [VerfasserIn]
Aghemo, Alessio [VerfasserIn]
Gerussi, Alessio [VerfasserIn]
Ramirez, Alfredo [VerfasserIn]
Braun, Alice [VerfasserIn]
Nebel, Almut [VerfasserIn]
Barreira, Ana [VerfasserIn]
Lleo, Ana [VerfasserIn]
Teles, Ana [VerfasserIn]
Kildal, Anders Benjamin [VerfasserIn]
Biondi, Andrea [VerfasserIn]
Caballero-Garralda, Andrea [VerfasserIn]
Ganna, Andrea [VerfasserIn]
Gori, Andrea [VerfasserIn]
Glück, Andreas [VerfasserIn]
Lind, Andreas [VerfasserIn]
Tanck, Anja [VerfasserIn]
Hinney, Anke [VerfasserIn]
Carreras Nolla, Anna [VerfasserIn]
Fracanzani, Anna Ludovica [VerfasserIn]
Peschuck, Anna [VerfasserIn]
Cavallero, Annalisa [VerfasserIn]
Dyrhol-Riise, Anne Ma [VerfasserIn]
Ruello, Antonella [VerfasserIn]
Julià, Antonio [VerfasserIn]
Muscatello, Antonio [VerfasserIn]
Pesenti, Antonio [VerfasserIn]
Voza, Antonio [VerfasserIn]
Rando-Segura, Ariadna [VerfasserIn]
Solier, Aurora [VerfasserIn]
Schmidt, Axel [VerfasserIn]
Cortes, Beatriz [VerfasserIn]
Mateos, Beatriz [VerfasserIn]
Nafria-Jimenez, Beatriz [VerfasserIn]
Schaefer, Benedikt [VerfasserIn]
Jensen, Björn [VerfasserIn]
Bellinghausen, Carla [VerfasserIn]
Maj, Carlo [VerfasserIn]
Ferrando, Carlos [VerfasserIn]
de la Horra, Carmen [VerfasserIn]
Quereda, Carmen [VerfasserIn]
Skurk, Carsten [VerfasserIn]
Thibeault, Charlotte [VerfasserIn]
Scollo, Chiara [VerfasserIn]
Herr, Christian [VerfasserIn]
Spinner, Christoph D [VerfasserIn]
Gassner, Christoph [VerfasserIn]
Lange, Christoph [VerfasserIn]
Hu, Cinzia [VerfasserIn]
Paccapelo, Cinzia [VerfasserIn]
Lehmann, Clara [VerfasserIn]
Angelini, Claudio [VerfasserIn]
Cappadona, Claudio [VerfasserIn]
Azuure, Clinton [VerfasserIn]
COVICAT study group, Aachen Study (COVAS) [VerfasserIn]
Bianco, Cristiana [VerfasserIn]
Cea, Cristina [VerfasserIn]
Sancho, Cristina [VerfasserIn]
Hoff, Dag Arne Lihaug [VerfasserIn]
Galimberti, Daniela [VerfasserIn]
Prati, Daniele [VerfasserIn]
Haschka, David [VerfasserIn]
Jiménez, David [VerfasserIn]
Pestaña, David [VerfasserIn]
Toapanta, David [VerfasserIn]
Muñiz-Diaz, Eduardo [VerfasserIn]
Azzolini, Elena [VerfasserIn]
Sandoval, Elena [VerfasserIn]
Binatti, Eleonora [VerfasserIn]
Scarpini, Elio [VerfasserIn]
Helbig, Elisa T [VerfasserIn]
Norwegian SARS-CoV-2 Study group [VerfasserIn]
Pa Study Group [VerfasserIn]
STORM Study group, The Humanitas Task Force, The Humanitas Gavazzeni Task Force [VerfasserIn]
et al [Sonstige Person]

Links:

Volltext

Themen:

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 30.11.2022

Date Revised 15.02.2023

published: Print

Citation Status MEDLINE

doi:

10.1093/hmg/ddac158

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM343691574