Dataset Information

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

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 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.

SUBMITTER: Degenhardt F

PROVIDER: S-EPMC9703941 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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

Degenhardt Frauke F Ellinghaus David D Juzenas Simonas S Lerga-Jaso Jon J Wendorff Mareike M Maya-Miles Douglas D Uellendahl-Werth Florian F ElAbd Hesham H Rühlemann Malte C MC Arora Jatin J Özer Onur O Lenning Ole Bernt OB Myhre Ronny R Vadla May Sissel MS Wacker Eike M EM Wienbrandt Lars L Blandino Ortiz Aaron A de Salazar Adolfo A Garrido Chercoles Adolfo A Palom Adriana A Ruiz Agustín A Garcia-Fernandez Alba-Estela AE Blanco-Grau Albert A Mantovani Alberto A Zanella Alberto A Holten Aleksander Rygh AR Mayer Alena A Bandera Alessandra A Cherubini Alessandro A Protti Alessandro A Aghemo Alessio A Gerussi Alessio A Ramirez Alfredo A Braun Alice A Nebel Almut A Barreira Ana A Lleo Ana A Teles Ana A Kildal Anders Benjamin AB Biondi Andrea A Caballero-Garralda Andrea A Ganna Andrea A Gori Andrea A Glück Andreas A Lind Andreas A Tanck Anja A Hinney Anke A Carreras Nolla Anna A Fracanzani Anna Ludovica AL Peschuck Anna A Cavallero Annalisa A Dyrhol-Riise Anne Ma AM Ruello Antonella A Julià Antonio A Muscatello Antonio A Pesenti Antonio A Voza Antonio A Rando-Segura Ariadna A Solier Aurora A Schmidt Axel A Cortes Beatriz B Mateos Beatriz B Nafria-Jimenez Beatriz B Schaefer Benedikt B Jensen Björn B Bellinghausen Carla C Maj Carlo C Ferrando Carlos C de la Horra Carmen C Quereda Carmen C Skurk Carsten C Thibeault Charlotte C Scollo Chiara C Herr Christian C Spinner Christoph D CD Gassner Christoph C Lange Christoph C Hu Cinzia C Paccapelo Cinzia C Lehmann Clara C Angelini Claudio C Cappadona Claudio C Azuure Clinton C Bianco Cristiana C Cea Cristina C Sancho Cristina C Hoff Dag Arne Lihaug DAL Galimberti Daniela D Prati Daniele D Haschka David D Jiménez David D Pestaña David D Toapanta David D Muñiz-Diaz Eduardo E Azzolini Elena E Sandoval Elena E Binatti Eleonora E Scarpini Elio E Helbig Elisa T ET Casalone Elisabetta E Urrechaga Eloisa E Paraboschi Elvezia Maria EM Pontali Emanuele E Reverter Enric E Calderón Enrique J EJ Navas Enrique E Solligård Erik E Contro Ernesto E Arana-Arri Eunate E Aziz Fátima F Garcia Federico F García Sánchez Félix F Ceriotti Ferruccio F Martinelli-Boneschi Filippo F Peyvandi Flora F Kurth Florian F Blasi Francesco F Malvestiti Francesco F Medrano Francisco J FJ Mesonero Francisco F Rodriguez-Frias Francisco F Hanses Frank F Müller Fredrik F Hemmrich-Stanisak Georg G Bellani Giacomo G Grasselli Giacomo G Pezzoli Gianni G Costantino Giorgio G Albano Giovanni G Cardamone Giulia G Bellelli Giuseppe G Citerio Giuseppe G Foti Giuseppe G Lamorte Giuseppe G Matullo Giuseppe G Baselli Guido G Kurihara Hayato H Neb Holger H My Ilaria I Kurth Ingo I Hernández Isabel I Pink Isabell I de Rojas Itziar I Galván-Femenia Iván I Holter Jan Cato JC Afset Jan Egil JE Heyckendorf Jan J Kässens Jan J Damås Jan Kristian JK Rybniker Jan J Altmüller Janine J Ampuero Javier J Martín Javier J Erdmann Jeanette J Banales Jesus M JM Badia Joan Ramon JR Dopazo Joaquin J Schneider Jochen J Bergan Jonas J Barretina Jordi J Walter Jörn J Hernández Quero Jose J Goikoetxea Josune J Delgado Juan J Guerrero Juan M JM Fazaal Julia J Kraft Julia J Schröder Julia J Risnes Kari K Banasik Karina K Müller Karl Erik KE Gaede Karoline I KI Garcia-Etxebarria Koldo K Tonby Kristian K Heggelund Lars L Izquierdo-Sanchez Laura L Bettini Laura Rachele LR Sumoy Lauro L Sander Leif Erik LE Lippert Lena J LJ Terranova Leonardo L Nkambule Lindokuhle L Knopp Lisa L Gustad Lise Tuset LT Garbarino Lucia L Santoro Luigi L Téllez Luis L Roade Luisa L Ostadreza Mahnoosh M Intxausti Maider M Kogevinas Manolis M Riveiro-Barciela Mar M Berger Marc M MM Schaefer Marco M Niemi Mari E K MEK Gutiérrez-Stampa María A MA Carrabba Maria M Figuera Basso Maria E ME Valsecchi Maria Grazia MG Hernandez-Tejero María M Vehreschild Maria J G T MJGT Manunta Maria M Acosta-Herrera Marialbert M D'Angiò Mariella M Baldini Marina M Cazzaniga Marina M Grimsrud Marit M MM Cornberg Markus M Nöthen Markus M MM Marquié Marta M Castoldi Massimo M Cordioli Mattia M Cecconi Maurizio M D'Amato Mauro M Augustin Max M Tomasi Melissa M Boada Mercè M Dreher Michael M Seilmaier Michael J MJ Joannidis Michael M Wittig Michael M Mazzocco Michela M Ciccarelli Michele M Rodríguez-Gandía Miguel M Bocciolone Monica M Miozzo Monica M Imaz Ayo Natale N Blay Natalia N Chueca Natalia N Montano Nicola N Braun Nicole N Ludwig Nicole N Marx Nikolaus N Martínez Nilda N Cornely Oliver A OA Witzke Oliver O Palmieri Orazio O Faverio Paola P Preatoni Paoletta P Bonfanti Paolo P Omodei Paolo P Tentorio Paolo P Castro Pedro P Rodrigues Pedro M PM España Pedro Pablo PP Hoffmann Per P Rosenstiel Philip P Schommers Philipp P Suwalski Phillip P de Pablo Raúl R Ferrer Ricard R Bals Robert R Gualtierotti Roberta R Gallego-Durán Rocío R Nieto Rosa R Carpani Rossana R Morilla Rubén R Badalamenti Salvatore S Haider Sammra S Ciesek Sandra S May Sandra S Bombace Sara S Marsal Sara S Pigazzini Sara S Klein Sebastian S Pelusi Serena S Wilfling Sibylle S Bosari Silvano S Volland Sonja S Brunak Søren S Raychaudhuri Soumya S Schreiber Stefan S Heilmann-Heimbach Stefanie S Aliberti Stefano S Ripke Stephan S Dudman Susanne S Wesse Tanja T Zheng Tenghao T Bahmer Thomas T Eggermann Thomas T Illig Thomas T Brenner Thorsten T Pumarola Tomas T Feldt Torsten T Folseraas Trine T Gonzalez Cejudo Trinidad T Landmesser Ulf U Protzer Ulrike U Hehr Ute U Rimoldi Valeria V Monzani Valter V Skogen Vegard V Keitel Verena V Kopfnagel Verena V Friaza Vicente V Andrade Victor V Moreno Victor V Albrecht Wolfgang W Peter Wolfgang W Poller Wolfgang W Farre Xavier X Yi Xiaoli X Wang Xiaomin X Khodamoradi Yascha Y Karadeniz Zehra Z Latiano Anna A Goerg Siegfried S Bacher Petra P Koehler Philipp P Tran Florian F Zoller Heinz H Schulte Eva C EC Heidecker Bettina B Ludwig Kerstin U KU Fernández Javier J Romero-Gómez Manuel M Albillos Agustín A Invernizzi Pietro P Buti Maria M Duga Stefano S Bujanda Luis L Hov Johannes R JR Lenz Tobias L TL Asselta Rosanna R de Cid Rafael R Valenti Luca L Karlsen Tom H TH Cáceres Mario M Franke Andre A

Human molecular genetics 20221101 23

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 ag ...[more]

PMID: 35848942

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Project description:BackgroundCalprotectin is an inflammatory marker mainly released by activated neutrophils that is increased in acute severe COVID-19. After initial recovery, some patients have persistent respiratory impairment with reduced diffusion capacity of the lungs for carbon monoxide (DLCO) months after infection. Underlying causes of this persistent impairment are unclear. We aimed to investigate the correlation between circulating calprotectin, persistent lung functional impairment and intensive care unit (ICU) stay after COVID-19 in two university hospital centres in Switzerland.MethodsCalprotectin levels were measured in serum from 124 patients (50% male) from the Bern cohort (post-ICU and non-ICU patients) and 68 (76% male) from the Lausanne cohort (only post-ICU patients) four months after COVID-19. Calprotectin was correlated with clinical parameters. Multivariate linear regression (MLR) was performed to evaluate the independent association of calprotectin in different models.ResultsOverall, we found that post-ICU patients, compared to non-ICU, were significantly older (age 59.4 ± 13.6 (Bern), 60.5 ± 12.0 (Lausanne) vs. 48.8 ± 13.4 years) and more obese (BMI 28.6 ± 4.5 and 29.1 ± 5.3 vs. 25.2 ± 6.0 kg/m2, respectively). 48% of patients from Lausanne and 44% of the post-ICU Bern cohort had arterial hypertension as a pre-existing comorbidity vs. only 10% in non-ICU patients. Four months after COVID-19 infection, DLCO was lower in post-ICU patients (75.96 ± 19.05% predicted Bern, 71.11 ± 18.50% Lausanne) compared to non-ICU (97.79 ± 21.70% predicted, p < 0.01). The post-ICU cohort in Lausanne had similar calprotectin levels when compared to the cohort in Bern (Bern 2.74 ± 1.15 µg/ml, Lausanne 2.49 ± 1.13 µg/ml vs. non-ICU 1.86 ± 1.02 µg/ml; p-value < 0.01). Calprotectin correlated negatively with DLCO (r= -0.290, p < 0.001) and the forced vital capacity (FVC) (r= -0.311, p < 0.001).ConclusionsSerum calprotectin is elevated in post-ICU patients in two independent cohorts and higher compared to non-ICU patients four months after COVID-19. In addition, there is a negative correlation between calprotectin levels and DLCO or FVC. The relationship between inflammation and lung functional impairment needs further investigations.Trial registrationNCT04581135.

Project description:BackgroundDespite a wealth of data from high-income countries, there is limited information on the distinct epidemiological patterns observed in diverse, densely populated regions within Latin America. This retrospective analysis of COVID-19's four major waves in Bogotá, Colombia, evaluates 1.77 million cases in detail.MethodsA comprehensive suite of statistical methods was employed. Transmission dynamics were assessed by estimating the instantaneous reproduction number R(t) , while variant-specific transmission advantages were estimated using multinomial logistic regression models. Disease severity was assessed through a suite of indicators: Hospitalisation Case Ratio (HCR), intensive care unit case ratio (ICU-CR), case fatality ratio (CFR), hospitalisation fatality ratio (HFR), and ICU fatality ratio (ICU-FR). Additionally, we analysed the distribution of hospitalisations, ICU admissions, and fatalities by age group and wave. We employed a Bayesian hierarchical model to capture epidemiological delays-such as onset-to-death, hospitalisation, and ICU admission durations to estimate hospital and ICU stay durations.ResultsOur findings reveal substantial variation in R(t) , with peaks exceeding 2.5 during the ancestral and Omicron waves. Over the course of the pandemic, we observed a 78% reduction in CFR, underscoring shifts in clinical severity. The third wave, associated with the Mu variant, recorded the highest case and death counts, alongside a decreased CFR, an elevated HFR, and a shift in the most affected age group towards younger populations. In contrast, the fourth wave, driven by the Omicron variant, exhibited the highest reproduction number and the lowest overall severity. This wave was characterised by a significant increase in pediatric hospitalisations. The study reveals a continued decline in the mean durations of hospital and ICU stays across the four waves, with hospital stays decreasing from 10.84 to 7.85 days and ICU stays dropping from 16.2 to 12.4 days.ConclusionsThis study reveals significant shifts in transmission and severity metrics-including mortality, hospitalisation, and ICU rates and stays-across age groups during Bogotá's four COVID-19 waves. These insights underscore the value of retrospective analyses to understand the pandemic's varied impact and inform public health strategies in diverse urban settings.

Dataset Information

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

Publications

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

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