Humans; Genome-Wide Association Study/methods; Genetic Predisposition to Disease; SARS-CoV-2; Genotype; COVID-19; Multidisciplinary
Abstract :
[en] The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10-8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10-8). A total of 113 variants were associated with survival at P-value < 1.0 × 10-5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways.
Disciplines :
Microbiology
Author, co-author :
Minnai, Francesca; Institute of Biomedical Technologies, National Research Council, Via F.lli Cervi, 93, 20054, Segrate, MI, Italy ; Department of Medical Biotechnology and Translational Medicine (BioMeTra), Università degli Studi di Milano, Milan, Italy
Biscarini, Filippo; Institute of Agricultural Biology and Biotechnology, National Research Council, Milan, Italy
Esposito, Martina; Institute of Biomedical Technologies, National Research Council, Via F.lli Cervi, 93, 20054, Segrate, MI, Italy
Dragani, Tommaso A; Aspidia S.R.L., Milan, Italy
Bujanda, Luis; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Biodonostia Health Research Institute, Universidad del País Vasco (UPV/EHU), San Sebastián, Spain
Rahmouni, Souad ; Université de Liège - ULiège > GIGA > GIGA Medical Genomics - Unit of Animal Genomics
Alarcón-Riquelme, Marta E; GENYO, University of Granada, Andalusian Regional Government, Granada, Spain ; Institute for Environmental Medicine, Karolinska Institute, Solna, Sweden
Bernardo, David; Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III (ISCIII), Madrid, Spain ; Mucosal Immunology Lab, Unit of Excellence, Institute of Biomedicine and Molecular Genetics (IBGM), University of Valladolid-CSIC, Valladolid, Spain
Carnero-Montoro, Elena; GENYO, University of Granada, Andalusian Regional Government, Granada, Spain ; University of Granada, Granada, Spain
Buti, Maria; Vall D'Hebron Institut de Recerca, Barcelona, Spain
Zeberg, Hugo; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Asselta, Rosanna; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI, Italy ; IRCCS Humanitas Research Hospital, Rozzano, MI, Italy
Romero-Gómez, Manuel; Digestive Diseases Unit and CiberehdVirgen del Rocío University HospitalInstitute of Biomedicine of Seville (HUVR/CSIC/US), University of Seville, Seville, Spain
GEN-COVID Multicenter Study
Fernandez-Cadenas, Israel; Stroke Pharmacogenomics and Genetics Group, Sant Pau Hospital Research Institute, Barcelona, Spain
Fallerini, Chiara; Medical Genetics, University of Siena, 53100, Siena, Italy ; Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, 53100, Siena, Italy
Zguro, Kristina; Medical Genetics, University of Siena, 53100, Siena, Italy ; Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, 53100, Siena, Italy
Croci, Susanna; Medical Genetics, University of Siena, 53100, Siena, Italy ; Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, 53100, Siena, Italy
Baldassarri, Margherita; Medical Genetics, University of Siena, 53100, Siena, Italy ; Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, 53100, Siena, Italy
Bruttini, Mirella; Medical Genetics, University of Siena, 53100, Siena, Italy ; Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, 53100, Siena, Italy ; Genetica Medica, Azienda Ospedaliero-Universitaria Senese, 53100, Siena, Italy
Furini, Simone; Dipartimento di Ingegneria dell'Energia Elettrica e dell'Informazione "Guglielmo Marconi", Alma Mater Studiorum - Università di Bologna, Bologna, Italy
Renieri, Alessandra; Medical Genetics, University of Siena, 53100, Siena, Italy ; Department of Medical Biotechnologies, Med Biotech Hub and Competence Center, University of Siena, 53100, Siena, Italy ; Genetica Medica, Azienda Ospedaliero-Universitaria Senese, 53100, Siena, Italy
Colombo, Francesca ; Institute of Biomedical Technologies, National Research Council, Via F.lli Cervi, 93, 20054, Segrate, MI, Italy. francesca.colombo@itb.cnr.it
