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
Green Submitted, Bronze
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