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Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality.
Nakanishi, Tomoko; Pigazzini, Sara; Degenhardt, Frauke; Cordioli, Mattia; Butler-Laporte, Guillaume; Maya-Miles, Douglas; Bujanda, Luis; Bouysran, Youssef; Niemi, Mari Ek; Palom, Adriana; Ellinghaus, David; Khan, Atlas; Martínez-Bueno, Manuel; Rolker, Selina; Amitrano, Sara; Roade Tato, Luisa; Fava, Francesca; Spinner, Christoph D; Prati, Daniele; Bernardo, David; Garcia, Federico; Darcis, Gilles; Fernández-Cadenas, Israel; Holter, Jan Cato; Banales, Jesus M; Frithiof, Robert; Kiryluk, Krzysztof; Duga, Stefano; Asselta, Rosanna; Pereira, Alexandre C; Romero-Gómez, Manuel; Nafría-Jiménez, Beatriz; Hov, Johannes R; Migeotte, Isabelle; Renieri, Alessandra; Planas, Anna M; Ludwig, Kerstin U; Buti, Maria; Rahmouni, Souad; Alarcón-Riquelme, Marta E; Schulte, Eva C; Franke, Andre; Karlsen, Tom H; Valenti, Luca; Zeberg, Hugo; Richards, J Brent; Ganna, Andrea.
  • Nakanishi T; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
  • Pigazzini S; Department of Human Genetics and.
  • Degenhardt F; Centre for Clinical Epidemiology, Department of Medicine, Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Cordioli M; Kyoto-McGill International Collaborative School in Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Butler-Laporte G; Japan Society for the Promotion of Science, Tokyo, Japan.
  • Maya-Miles D; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
  • Bujanda L; University of Milano-Bicocca, Milano, Italy.
  • Bouysran Y; Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany.
  • Niemi ME; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
  • Palom A; Centre for Clinical Epidemiology, Department of Medicine, Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Quebec, Canada.
  • Ellinghaus D; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Quebec, Canada.
  • Khan A; Digestive Diseases Unit, Virgen del Rocio University Hospital, Institute of Biomedicine of Seville, University of Seville, Seville, Spain.
  • Martínez-Bueno M; Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
  • Rolker S; Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), CIBERehd, Ikerbasque, San Sebastian, Spain.
  • Amitrano S; Centre de Génétique Humaine, Hôpital Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium.
  • Roade Tato L; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
  • Fava F; Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
  • Spinner CD; Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany.
  • Prati D; Novo Nordisk Foundation Center for Protein Research, Disease Systems Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Bernardo D; Division of Nephrology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
  • Garcia F; GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain.
  • Darcis G; nstitute of Human Genetics, University Hospital Bonn, Medical Faculty University of Bonn, Bonn, Germany.
  • Fernández-Cadenas I; Genetica Medica, Azienda Ospedaliero-Universitaria Senese, Siena, Italy.
  • Holter JC; Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
  • Banales JM; Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
  • Frithiof R; Departament de Medicina: Bellaterra, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • Kiryluk K; Genetica Medica, Azienda Ospedaliero-Universitaria Senese, Siena, Italy.
  • Duga S; Medical Genetics and.
  • Asselta R; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Italy.
  • Nafría-Jiménez B; Technical University of Munich, School of Medicine, University Hospital Rechts der Isar, Department of Internal Medicine II, Munich, Germany.
  • Hov JR; Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy.
  • Migeotte I; Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
  • Renieri A; Mucosal Immunology Lab, Unit of Excellence Institute of Biomedicine and Molecular Genetics (IBGM), University of Valladolid-CSIC, Valladolid, Spain.
  • Planas AM; Hospital Universitario Clinico San Cecilio, Granada, Spain.
  • Ludwig KU; Instituto de Investigación Ibs.Granada, Granada, Spain.
  • Buti M; University of Liege, GIGA-Insitute, Liege, Belgium.
  • Rahmouni S; Liege University Hospital (CHU of Liege), Liege, Belgium.
  • Alarcón-Riquelme ME; Stroke Pharmacogenomics and Genetics Group, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
  • Schulte EC; Department of Microbiology, Oslo University Hospital, Oslo, Norway.
  • Franke A; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • Karlsen TH; Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), CIBERehd, Ikerbasque, San Sebastian, Spain.
  • Valenti L; Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain.
  • Zeberg H; Department of Surgical Sciences, Anaesthesiology and Intensive Care Medicine, Uppsala University, Uppsala, Sweden.
  • Richards JB; Division of Nephrology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
  • Ganna A; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
J Clin Invest ; 131(23)2021 12 01.
Article in English | MEDLINE | ID: covidwho-1546628
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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ABSTRACT
BackgroundThere is considerable variability in COVID-19 outcomes among younger adults, and some of this variation may be due to genetic predisposition.MethodsWe combined individual level data from 13,888 COVID-19 patients (n = 7185 hospitalized) from 17 cohorts in 9 countries to assess the association of the major common COVID-19 genetic risk factor (chromosome 3 locus tagged by rs10490770) with mortality, COVID-19-related complications, and laboratory values. We next performed metaanalyses using FinnGen and the Columbia University COVID-19 Biobank.ResultsWe found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (HR, 1.4; 95% CI, 1.2-1.7). Risk allele carriers had increased odds of several COVID-19 complications severe respiratory failure (OR, 2.1; 95% CI, 1.6-2.6), venous thromboembolism (OR, 1.7; 95% CI, 1.2-2.4), and hepatic injury (OR, 1.5; 95% CI, 1.2-2.0). Risk allele carriers age 60 years and younger had higher odds of death or severe respiratory failure (OR, 2.7; 95% CI, 1.8-3.9) compared with those of more than 60 years (OR, 1.5; 95% CI, 1.2-1.8; interaction, P = 0.038). Among individuals 60 years and younger who died or experienced severe respiratory failure, 32.3% were risk-variant carriers compared with 13.9% of those not experiencing these outcomes. This risk variant improved the prediction of death or severe respiratory failure similarly to, or better than, most established clinical risk factors.ConclusionsThe major common COVID-19 genetic risk factor is associated with increased risks of morbidity and mortality, which are more pronounced among individuals 60 years or younger. The effect was similar in magnitude and more common than most established clinical risk factors, suggesting potential implications for future clinical risk management.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Polymorphism, Genetic / Chromosomes, Human, Pair 3 / Alleles / Genetic Loci / Gene Frequency / SARS-CoV-2 / COVID-19 Type of study: Controlled clinical trial / Etiology study / Prognostic study / Reviews / Risk factors Topics: Variants Limits: Aged / Female / Humans / Male / Middle aged Language: English Year: 2021 Document Type: Article Affiliation country: JCI152386

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Polymorphism, Genetic / Chromosomes, Human, Pair 3 / Alleles / Genetic Loci / Gene Frequency / SARS-CoV-2 / COVID-19 Type of study: Controlled clinical trial / Etiology study / Prognostic study / Reviews / Risk factors Topics: Variants Limits: Aged / Female / Humans / Male / Middle aged Language: English Year: 2021 Document Type: Article Affiliation country: JCI152386