A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death.

Autor: Minnai F; 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 F; Institute of Agricultural Biology and Biotechnology, National Research Council, Milan, Italy., Esposito M; Institute of Biomedical Technologies, National Research Council, Via F.lli Cervi, 93, 20054, Segrate, MI, Italy., Dragani TA; Aspidia S.R.L., Milan, Italy., Bujanda L; 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 S; GIGA-Medical Genomics Unit, Uliege, Liege, Belgium., Alarcón-Riquelme ME; GENYO, University of Granada, Andalusian Regional Government, Granada, Spain.; Institute for Environmental Medicine, Karolinska Institute, Solna, Sweden., Bernardo D; 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 E; GENYO, University of Granada, Andalusian Regional Government, Granada, Spain.; University of Granada, Granada, Spain., Buti M; Vall D'Hebron Institut de Recerca, Barcelona, Spain., Zeberg H; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Asselta R; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI, Italy.; IRCCS Humanitas Research Hospital, Rozzano, MI, Italy., Romero-Gómez M; Digestive Diseases Unit and CiberehdVirgen del Rocío University HospitalInstitute of Biomedicine of Seville (HUVR/CSIC/US), University of Seville, Seville, Spain., Fernandez-Cadenas I; Stroke Pharmacogenomics and Genetics Group, Sant Pau Hospital Research Institute, Barcelona, Spain., Fallerini C; 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 K; 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 S; 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 M; 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 M; 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 S; Dipartimento di Ingegneria dell'Energia Elettrica e dell'Informazione 'Guglielmo Marconi', Alma Mater Studiorum - Università di Bologna, Bologna, Italy., Renieri A; 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 F; Institute of Biomedical Technologies, National Research Council, Via F.lli Cervi, 93, 20054, Segrate, MI, Italy. francesca.colombo@itb.cnr.it.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Feb 06; Vol. 14 (1), pp. 3000. Date of Electronic Publication: 2024 Feb 06.
DOI: 10.1038/s41598-024-53310-x
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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