Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality


Por: Nakanishi, T, Pigazzini, S, Degenhardt, F, Cordioli, M, Butler-Laporte, G, Maya-Miles, D, Bujanda, L, Bouysran, Y, Niemi, MEK, Palom, A, Ellinghaus, D, Khan, A, Martinez-Bueno, M, Rolker, S, Amitrano, S, Tato, LR, Fava, F, Spinner, CD, Prati, D, Bernardo, D, Garcia, F, Darcis, G, Fernandez-Cadenas, I, Holter, JC, Banales, JM, Frithiof, R, Kiryluk, K, Duga, S, Asselta, R, Pereira, AC, Romero-Gomez, M, Nafria-Jimenez, B, Hov, JR, Migeotte, I, Renieri, A, Planas, AM, Ludwig, KU, Buti, M, Rahmouni, S, Alarcon-Riquelme, ME, Schulte, EC, Franke, A, Karlsen, TH, Valenti, L, Zeberg, H, Richards, JB, Ganna, A, FinnGen

Publicada: 1 dic 2021
Resumen:
BACKGROUND. There is considerable variability in COVID-19 outcomes among younger adults, and some of this variation may be due to genetic predisposition. METHODS. We 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. RESULTS. We 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. CONCLUSIONS. The 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.

Filiaciones:
Nakanishi, T:
 Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland

 McGill Univ, Dept Human Genet, Montreal, PQ, Canada

 McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada

 Kyoto Univ, Grad Sch Med, Kyoto McGill Int Collaborat Sch Genom Med, Kyoto, Japan

 Japan Soc Promot Sci, Tokyo, Japan

Pigazzini, S:
 Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland

 Univ Milano Bicocca, Milan, Italy

Degenhardt, F:
 Univ Kiel, Inst Clin Mol Biol, Kiel, Germany

Cordioli, M:
 Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland

Butler-Laporte, G:
 McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada

 McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada

Maya-Miles, D:
 Univ Seville, Virgen del Rocio Univ Hosp, Inst Biomed Seville, Digest Dis Unit, Seville, Spain

 Inst Salud Carlos Iii ISCIII, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

Bujanda, L:
 Univ Basque Country UPV EHU, Biodonostia Hlth Res Inst, Dept Liver & Gastrointestinal Dis, Donostia Univ Hosp,CIBERehd,Ikerbasque, San Sebastian, Spain

Bouysran, Y:
 Univ Libre Bruxelles ULB, Ctr Genet Humaine, Hop Erasme, Brussels, Belgium

Niemi, MEK:
 Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland

Palom, A:
 Hosp Univ Vall dHebron, Dept Internal Med, Liver Unit, Vall dHebron Barcelona Hosp Campus, Barcelona, Spain

 Univ Autonoma Barcelona, Dept Med Bellatera, Barcelona, Spain

 Vall dHebron Inst Recerca VHIR, Liver Dis, Barcelona, Spain

Ellinghaus, D:
 Univ Kiel, Inst Clin Mol Biol, Kiel, Germany

 Univ Copenhagen, Novo Nordisk Fdn Ctr Prot Res, Fac Hlth & Med Sci, Dis Syst Biol, Copenhagen, Denmark

Khan, A:
 Columbia Univ, Vagelos Coll Phys & Surg, Dept Med, Div Nephrol, New York, NY USA

Martinez-Bueno, M:
 Univ Granada, GENYO, Ctr Genom & Oncol Res Pfizer, Andalusian Reg Govt, Granada, Spain

Rolker, S:
 Univ Bonn, Med Fac, Inst Human Genet, Univ Hosp Bonn, Bonn, Germany

Amitrano, S:
 Azienda Osped Univ Senese, Genet Med, Siena, Italy

Tato, LR:
 Inst Salud Carlos Iii ISCIII, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

 Hosp Univ Vall dHebron, Dept Internal Med, Liver Unit, Vall dHebron Barcelona Hosp Campus, Barcelona, Spain

 Univ Autonoma Barcelona, Dept Med Bellatera, Barcelona, Spain

Fava, F:
 Azienda Osped Univ Senese, Genet Med, Siena, Italy

 Univ Siena, Med Genet, Siena, Italy

 Univ Siena, Med Biotech Hub, Dept Med Biotechnol, Siena, Italy

 Univ Siena, Competence Ctr, Dept Med Biotechnol, Siena, Italy

Spinner, CD:
 Tech Univ Munich, Univ Hosp Rechts Isar, Sch Med, Dept Internal Med 2, Munich, Germany

Prati, D:
 Univ Milan, Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dept Transfus Med & Hematol, Milan, Italy

Bernardo, D:
 Inst Salud Carlos Iii ISCIII, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

 Univ Valladolid, Inst Biomed & Mol Genet IBGM, Mucosal Immunol Lab, CSIC, Valladolid, Spain

Garcia, F:
 Hosp Univ Clin San Cecilio, Granada, Spain

 Inst Invest Ibs Granada, Granada, Spain

Darcis, G:
 Univ Liege, GIGA Insitute, Liege, Belgium

 Liege Univ Hosp CHU Liege, Liege, Belgium

Fernandez-Cadenas, I:
 Biomed Res Inst St Pau IIB St Pau, Stroke Pharmacogen & Genet Grp, Barcelona, Spain

Holter, JC:
 Oslo Univ Hosp, Dept Microbiol, Oslo, Norway

 Univ Oslo, Inst Clin Med, Oslo, Norway

Banales, JM:
 Univ Basque Country UPV EHU, Biodonostia Hlth Res Inst, Dept Liver & Gastrointestinal Dis, Donostia Univ Hosp,CIBERehd,Ikerbasque, San Sebastian, Spain

 Univ Navarra, Sch Sci, Dept Biochem & Genet, Pamplona, Spain

Frithiof, R:
 Uppsala Univ, Dept Surg Sci Anaesthesiol & Intens Care Med, Uppsala, Sweden

Kiryluk, K:
 Columbia Univ, Vagelos Coll Phys & Surg, Dept Med, Div Nephrol, New York, NY USA

Duga, S:
 Humanitas Univ, Dept Biomed Sci, Milan, Italy

 IRCCS Humanitas Res Hosp, Milan, Italy

Asselta, R:
 Humanitas Univ, Dept Biomed Sci, Milan, Italy

 IRCCS Humanitas Res Hosp, Milan, Italy

Pereira, AC:
 Univ Sao Paulo, Med Sch, Heart Inst InCor, Sao Paulo, Brazil

Romero-Gomez, M:
 Univ Seville, Virgen del Rocio Univ Hosp, Inst Biomed Seville, Digest Dis Unit, Seville, Spain

 Inst Salud Carlos Iii ISCIII, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

Nafria-Jimenez, B:
 Osakidetza Basque Hlth Serv, Donostialdea Integrated Hlth Org, Clin Biochem Dept, Sebastian, Spain

Hov, JR:
 Oslo Univ Hosp, Dept Microbiol, Oslo, Norway

 Oslo Univ Hosp, Norwegian PSC Res Ctr, Oslo, Norway

 Oslo Univ Hosp, Sect Gastroenterol, Dept Transplantat Med, Oslo, Norway

 Oslo Univ Hosp, Res Inst Internal Med, Oslo, Norway

Migeotte, I:
 Univ Libre Bruxelles ULB, Ctr Genet Humaine, Hop Erasme, Brussels, Belgium

 Fonds Rech Sci FNRS, Brussels, Belgium

Renieri, A:
 Azienda Osped Univ Senese, Genet Med, Siena, Italy

 Univ Siena, Med Genet, Siena, Italy

 Univ Siena, Med Biotech Hub, Dept Med Biotechnol, Siena, Italy

 Univ Siena, Competence Ctr, Dept Med Biotechnol, Siena, Italy

Planas, AM:
 Natl Spanish Res Council CSIC, Inst Biomed Researhc Barcelona IIBB, Barcelona, Spain

 Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain

Ludwig, KU:
 Univ Bonn, Med Fac, Inst Human Genet, Univ Hosp Bonn, Bonn, Germany

Buti, M:
 Inst Salud Carlos Iii ISCIII, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain

 Hosp Univ Vall dHebron, Dept Internal Med, Liver Unit, Vall dHebron Barcelona Hosp Campus, Barcelona, Spain

 Univ Autonoma Barcelona, Dept Med Bellatera, Barcelona, Spain

Rahmouni, S:
 Inst Invest Ibs Granada, Granada, Spain

Alarcon-Riquelme, ME:
 Univ Granada, GENYO, Ctr Genom & Oncol Res Pfizer, Andalusian Reg Govt, Granada, Spain

 Karolinska Inst, Inst Environm Med, Solna, Sweden

Schulte, EC:
 Tech Univ Munich, Inst Virol, Helmholtz Zentrum Munchen, Munich, Germany

 LMU Munich Univ, Univ Hosp, Inst Psychiat Phen & Genom, Munich, Germany

 LMU Munich Univ, Univ Hosp, Dept Psychiat, Munich, Germany

Franke, A:
 Univ Kiel, Inst Clin Mol Biol, Kiel, Germany

 Univ Hosp Schleswig Holstein, Campus Kiel, Kiel, Germany

Karlsen, TH:
 Univ Oslo, Inst Clin Med, Oslo, Norway

 Oslo Univ Hosp, Norwegian PSC Res Ctr, Oslo, Norway

 Oslo Univ Hosp, Sect Gastroenterol, Dept Transplantat Med, Oslo, Norway

 Oslo Univ Hosp, Res Inst Internal Med, Oslo, Norway

Valenti, L:
 Univ Milan, Dept Pathophysiol & Transplantat, Milan, Italy

 Fdn IRCCS Ca Granda Osped Maggiore Policlin, Dept Transfus Med & Hematol, Precis Med, Milan, Italy

Zeberg, H:
 Karolinska Inst, Dept Neurosci, Stockholm, Sweden

 Max Planck Inst Evolutionary Anthropol, Leipzig, Germany

Richards, JB:
 McGill Univ, Dept Human Genet, Montreal, PQ, Canada

 McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada

 Univ Seville, Virgen del Rocio Univ Hosp, Inst Biomed Seville, Digest Dis Unit, Seville, Spain

 Kings Coll London, Dept Twin Res, London, England

Ganna, A:
 Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland

 Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA
ISSN: 00219738





JOURNAL OF CLINICAL INVESTIGATION
Editorial
AMER SOC CLINICAL INVESTIGATION INC, 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA, Estados Unidos America
Tipo de documento: Article
Volumen: 131 Número: 23
Páginas:
WOS Id: 000726717300012
ID de PubMed: 33758887
imagen Green Submitted, Bronze

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