Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality
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.
| Errataetall: | |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:131 |
|---|---|
| Enthalten in: |
The Journal of clinical investigation - 131(2021), 23 vom: 01. Dez. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Nakanishi, Tomoko [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
COVID-19 |
|---|
| Anmerkungen: |
Date Completed 13.12.2021 Date Revised 02.03.2022 published: Print UpdateOf: medRxiv. 2021 Mar 12;:. - PMID 33758887 Citation Status MEDLINE |
|---|
| doi: |
10.1172/JCI152386 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM33138695X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM33138695X | ||
| 003 | DE-627 | ||
| 005 | 20231225213340.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1172/JCI152386 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1104.xml |
| 035 | |a (DE-627)NLM33138695X | ||
| 035 | |a (NLM)34597274 | ||
| 035 | |a (PII)e152386 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Nakanishi, Tomoko |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 13.12.2021 | ||
| 500 | |a Date Revised 02.03.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a UpdateOf: medRxiv. 2021 Mar 12;:. - PMID 33758887 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Clinical Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a Genetic variation | |
| 650 | 4 | |a Genetics | |
| 700 | 1 | |a Pigazzini, Sara |e verfasserin |4 aut | |
| 700 | 1 | |a Degenhardt, Frauke |e verfasserin |4 aut | |
| 700 | 1 | |a Cordioli, Mattia |e verfasserin |4 aut | |
| 700 | 1 | |a Butler-Laporte, Guillaume |e verfasserin |4 aut | |
| 700 | 1 | |a Maya-Miles, Douglas |e verfasserin |4 aut | |
| 700 | 1 | |a Bujanda, Luis |e verfasserin |4 aut | |
| 700 | 1 | |a Bouysran, Youssef |e verfasserin |4 aut | |
| 700 | 1 | |a Niemi, Mari Ek |e verfasserin |4 aut | |
| 700 | 1 | |a Palom, Adriana |e verfasserin |4 aut | |
| 700 | 1 | |a Ellinghaus, David |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Atlas |e verfasserin |4 aut | |
| 700 | 1 | |a Martínez-Bueno, Manuel |e verfasserin |4 aut | |
| 700 | 1 | |a Rolker, Selina |e verfasserin |4 aut | |
| 700 | 1 | |a Amitrano, Sara |e verfasserin |4 aut | |
| 700 | 1 | |a Roade Tato, Luisa |e verfasserin |4 aut | |
| 700 | 1 | |a Fava, Francesca |e verfasserin |4 aut | |
| 700 | 0 | |a FinnGen |e verfasserin |4 aut | |
| 700 | 0 | |a COVID-19 Host Genetics Initiative (HGI) |e verfasserin |4 aut | |
| 700 | 1 | |a Spinner, Christoph D |e verfasserin |4 aut | |
| 700 | 1 | |a Prati, Daniele |e verfasserin |4 aut | |
| 700 | 1 | |a Bernardo, David |e verfasserin |4 aut | |
| 700 | 1 | |a Garcia, Federico |e verfasserin |4 aut | |
| 700 | 1 | |a Darcis, Gilles |e verfasserin |4 aut | |
| 700 | 1 | |a Fernández-Cadenas, Israel |e verfasserin |4 aut | |
| 700 | 1 | |a Holter, Jan Cato |e verfasserin |4 aut | |
| 700 | 1 | |a Banales, Jesus M |e verfasserin |4 aut | |
| 700 | 1 | |a Frithiof, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Kiryluk, Krzysztof |e verfasserin |4 aut | |
| 700 | 1 | |a Duga, Stefano |e verfasserin |4 aut | |
| 700 | 1 | |a Asselta, Rosanna |e verfasserin |4 aut | |
| 700 | 1 | |a Pereira, Alexandre C |e verfasserin |4 aut | |
| 700 | 1 | |a Romero-Gómez, Manuel |e verfasserin |4 aut | |
| 700 | 1 | |a Nafría-Jiménez, Beatriz |e verfasserin |4 aut | |
| 700 | 1 | |a Hov, Johannes R |e verfasserin |4 aut | |
| 700 | 1 | |a Migeotte, Isabelle |e verfasserin |4 aut | |
| 700 | 1 | |a Renieri, Alessandra |e verfasserin |4 aut | |
| 700 | 1 | |a Planas, Anna M |e verfasserin |4 aut | |
| 700 | 1 | |a Ludwig, Kerstin U |e verfasserin |4 aut | |
| 700 | 1 | |a Buti, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Rahmouni, Souad |e verfasserin |4 aut | |
| 700 | 1 | |a Alarcón-Riquelme, Marta E |e verfasserin |4 aut | |
| 700 | 1 | |a Schulte, Eva C |e verfasserin |4 aut | |
| 700 | 1 | |a Franke, Andre |e verfasserin |4 aut | |
| 700 | 1 | |a Karlsen, Tom H |e verfasserin |4 aut | |
| 700 | 1 | |a Valenti, Luca |e verfasserin |4 aut | |
| 700 | 1 | |a Zeberg, Hugo |e verfasserin |4 aut | |
| 700 | 1 | |a Richards, J Brent |e verfasserin |4 aut | |
| 700 | 1 | |a Ganna, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Rando, Ariadna |e investigator |4 oth | |
| 700 | 1 | |a Benetti, Elisa |e investigator |4 oth | |
| 700 | 1 | |a Menon, Amritha |e investigator |4 oth | |
| 700 | 1 | |a So, Yat S |e investigator |4 oth | |
| 700 | 1 | |a Goldstein, David B |e investigator |4 oth | |
| 700 | 1 | |a O'Byrne, Sheila M |e investigator |4 oth | |
| 700 | 1 | |a Nandakumar, Renu |e investigator |4 oth | |
| 700 | 1 | |a Lipcsey, Miklos |e investigator |4 oth | |
| 700 | 1 | |a Hultström, Michael |e investigator |4 oth | |
| 700 | 1 | |a Bergqvist, Anders |e investigator |4 oth | |
| 700 | 1 | |a Odeberg-Wernerman, Suzanne |e investigator |4 oth | |
| 700 | 1 | |a Ampuero, Javier |e investigator |4 oth | |
| 700 | 1 | |a Gallego-Durán, Rocío |e investigator |4 oth | |
| 700 | 1 | |a de Salazar, Adolfo |e investigator |4 oth | |
| 700 | 1 | |a Hernández Quero, Jose |e investigator |4 oth | |
| 700 | 1 | |a Perez-Tur, Jordi |e investigator |4 oth | |
| 700 | 1 | |a Protzer, Ulrike |e investigator |4 oth | |
| 700 | 1 | |a Gonzalez Cejudo, Trinidad |e investigator |4 oth | |
| 700 | 1 | |a Tamayo, Eduardo |e investigator |4 oth | |
| 700 | 1 | |a Arana, Eunate |e investigator |4 oth | |
| 700 | 1 | |a Imaz Ayo, Natale |e investigator |4 oth | |
| 700 | 1 | |a Rodrigues, Pedro M |e investigator |4 oth | |
| 700 | 1 | |a Izquierdo, Laura |e investigator |4 oth | |
| 700 | 1 | |a Dopazo, Joaquín |e investigator |4 oth | |
| 700 | 1 | |a Aarem, Jeanette |e investigator |4 oth | |
| 700 | 1 | |a Mathisen, Åse-Berit |e investigator |4 oth | |
| 700 | 1 | |a Busson, Adeline |e investigator |4 oth | |
| 700 | 1 | |a Peyrassol, Xavier |e investigator |4 oth | |
| 700 | 1 | |a Wilkin, Françoise |e investigator |4 oth | |
| 700 | 1 | |a Pichon, Bruno |e investigator |4 oth | |
| 700 | 1 | |a Smits, Guillaume |e investigator |4 oth | |
| 700 | 1 | |a Vandernoot, Isabelle |e investigator |4 oth | |
| 700 | 1 | |a Tiembe, Nicky |e investigator |4 oth | |
| 700 | 1 | |a Riveiro-Barciela, Mar |e investigator |4 oth | |
| 700 | 1 | |a Rodriguez-Frias, Francisco |e investigator |4 oth | |
| 700 | 1 | |a Guntz, Julien |e investigator |4 oth | |
| 700 | 1 | |a Vaghi, Massimo |e investigator |4 oth | |
| 700 | 1 | |a Parzibut, Gilles |e investigator |4 oth | |
| 700 | 1 | |a Meuris, Christelle |e investigator |4 oth | |
| 700 | 1 | |a Thys, Marie |e investigator |4 oth | |
| 700 | 1 | |a Jacques, Jessica |e investigator |4 oth | |
| 700 | 1 | |a Léonard, Philippe |e investigator |4 oth | |
| 700 | 1 | |a Frippiat, Frederic |e investigator |4 oth | |
| 700 | 1 | |a Giot, Jean-Baptiste |e investigator |4 oth | |
| 700 | 1 | |a Sauvage, Anne-Sophie |e investigator |4 oth | |
| 700 | 1 | |a von Frenckell, Christian |e investigator |4 oth | |
| 700 | 1 | |a Lambermont, Bernard |e investigator |4 oth | |
| 700 | 1 | |a Malaise, Olivier |e investigator |4 oth | |
| 700 | 1 | |a Bovy, Christophe |e investigator |4 oth | |
| 700 | 1 | |a Bouquegneau, Antoine |e investigator |4 oth | |
| 700 | 1 | |a Moutschen, Michel |e investigator |4 oth | |
| 700 | 1 | |a Misset, Benoit |e investigator |4 oth | |
| 700 | 1 | |a Guiot, Julien |e investigator |4 oth | |
| 700 | 1 | |a Marx, Nikolaus |e investigator |4 oth | |
| 700 | 1 | |a Caldarelli, Gian Piero |e investigator |4 oth | |
| 700 | 1 | |a Ognibene, Agostino |e investigator |4 oth | |
| 700 | 1 | |a Pancrazzi, Alessandro |e investigator |4 oth | |
| 700 | 1 | |a Lorubbio, Maria |e investigator |4 oth | |
| 700 | 1 | |a Panese, Sandro |e investigator |4 oth | |
| 700 | 1 | |a Raggi, Pamela |e investigator |4 oth | |
| 700 | 1 | |a Marciano, Carmen |e investigator |4 oth | |
| 700 | 1 | |a Perna, Rita |e investigator |4 oth | |
| 700 | 1 | |a Stella, Alessandra |e investigator |4 oth | |
| 700 | 1 | |a Biscarini, Filippo |e investigator |4 oth | |
| 700 | 1 | |a Altmüller, Janine |e investigator |4 oth | |
| 700 | 1 | |a Capitani, Katia |e investigator |4 oth | |
| 700 | 1 | |a Lehmann, Clara |e investigator |4 oth | |
| 700 | 1 | |a Schommers, Philipp |e investigator |4 oth | |
| 700 | 1 | |a Augustin, Max |e investigator |4 oth | |
| 700 | 1 | |a Rybniker, Jan |e investigator |4 oth | |
| 700 | 1 | |a Rygh Holten, Aleksander |e investigator |4 oth | |
| 700 | 1 | |a Girardis, Massimo |e investigator |4 oth | |
| 700 | 1 | |a Venturelli, Sophie |e investigator |4 oth | |
| 700 | 1 | |a Busani, Stefano |e investigator |4 oth | |
| 700 | 1 | |a Kildal, Anders Benjamin |e investigator |4 oth | |
| 700 | 1 | |a Garcia-Fernandez, Alba-Estela |e investigator |4 oth | |
| 700 | 1 | |a Caballero-Garralda, Andrea |e investigator |4 oth | |
| 700 | 1 | |a Siano, Matteo |e investigator |4 oth | |
| 700 | 1 | |a Gabrieli, Arianna |e investigator |4 oth | |
| 700 | 1 | |a Sengupta, Soumitra |e investigator |4 oth | |
| 700 | 1 | |a Cardamone, Giulia |e investigator |4 oth | |
| 700 | 1 | |a Cappadona, Claudio |e investigator |4 oth | |
| 700 | 1 | |a Rimoldi, Valeria |e investigator |4 oth | |
| 700 | 1 | |a Mantovani, Alberto |e investigator |4 oth | |
| 700 | 1 | |a Protti, Alessandro |e investigator |4 oth | |
| 700 | 1 | |a Aghemo, Alessio |e investigator |4 oth | |
| 700 | 1 | |a Lleo, Ana |e investigator |4 oth | |
| 700 | 1 | |a Azzolini, Elena |e investigator |4 oth | |
| 700 | 1 | |a Paraboschi, Elvezia Maria |e investigator |4 oth | |
| 700 | 1 | |a My, Ilaria |e investigator |4 oth | |
| 700 | 1 | |a Cecconi, Maurizio |e investigator |4 oth | |
| 700 | 1 | |a Ionita-Laza, Iuliana |e investigator |4 oth | |
| 700 | 1 | |a Valente, Serafina |e investigator |4 oth | |
| 700 | 1 | |a Gravrok, Berit |e investigator |4 oth | |
| 700 | 1 | |a Ceri, Stefano |e investigator |4 oth | |
| 700 | 1 | |a Pinoli, Pietro |e investigator |4 oth | |
| 700 | 1 | |a Afilalo, Marc |e investigator |4 oth | |
| 700 | 1 | |a Spargi, Genni |e investigator |4 oth | |
| 700 | 1 | |a Corridi, Marta |e investigator |4 oth | |
| 700 | 1 | |a Cornberg, Markus |e investigator |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of clinical investigation |d 1924 |g 131(2021), 23 vom: 01. Dez. |w (DE-627)NLM000005487 |x 1558-8238 |7 nnns |
| 773 | 1 | 8 | |g volume:131 |g year:2021 |g number:23 |g day:01 |g month:12 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1172/JCI152386 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 131 |j 2021 |e 23 |b 01 |c 12 | ||