Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality.
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.
Overview publication
| Title | Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality. |
| Date | 2021-12-01 |
| Issue name | The Journal of clinical investigation |
| Issue number | v131.23 |
| DOI | 10.1172/JCI152386 |
| PubMed | 34597274 |
| Authors | |
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Cappadona C, Rimoldi V, Mantovani A, Protti A, Aghemo A, Lleo A, Azzolini E, Paraboschi EM, My I, Cecconi M, Ionita-Laza I, Valente S, Gravrok B, Ceri S, Pinoli P, Afilalo M, Spargi G, Corridi M, Cornberg M, Knopp L, Keitel V, Jensen B, Feldt T, D'Arminio Monforte A, Merlini E, Gaia Miraglia F, Bassetti M, Castelli F, Quiros-Roldan E, Degli Antoni M, Jenum S, Stiksrud B, Hesstvedt L, Pettersen F, Ormaasen V, Røstad K, Skeie L, Nur S, Reikvam DH, Egeland Christensen E, Jøntvedt Jørgensen M, Aballi S, Aarberg Lund KM, Scotton PG, Andretta F, Skogen V, Ferrer R, Zucchi P, Parravicini P, Øverstad S, Garcia-Etxebarria K, Picchiotti N, Cossarizza A, Karlsson P, Larsson A, Aucella F, Mazzei MA, Guerrini S, Schurr E, Shang N, Wang C, Gharavi AG, Reilly MP, Bianchi F, Perrella A, Daryl Tylden G, Quist-Paulsen E, Kaur Johal S, Steffensen A, Zanella I, Russo R, Andolfo I, Iolascon A, Capasso M, Merla G, Parisi SG, Baratti S, Pendrick D, Hod E, Chung W, Dreher M, Pink I, Bandini M, Spagnesi M, Piacentini P, Desanctis E, Cappelli S, Halstensen AM, Brynildsen J, Bergan J, Martinelli E, Nencioni C, Croci L, Tacconi D, Spertilli C, Scala R, Guidelli L, Gradin A, Galien S, Rubertsson S, Danielsson EA, Hanslin K, Luther T, Rosén J, Bulow S, Von Seth M, Kawati R, Ghanima W, Anedda F, Marcantonio S, Scolletta S, Franchi F, Feri M, Donati A, Klouman Bekken G, Hermann A, Opsand H, Martin Woll B, Müller KE, Bogen M, Austad C, Fabbiani M, Rossetti B, Dyrhol-Riise AM, Tonby K, Bachetti T, Mantovani S, Umberto Mondelli M, Vecchia M, Bruno R, Carella M, Castori M, Trotta T, Giannattasio F, Coiro G, Ludovisi S, Baselli G, Paccapelo C, Ceriotti F, Terranova L, Santoro L, Scudeller L, Carrabba M, Baldini M, Monzani V, Zanella A, Bandera A, Gori A, Ludovica Fracanzani A, Pesenti A, Martinelli-Boneschi F, Peyvandi F, Grasselli G, Costantino G, Miozzo M, Montano N, Gualtierotti R, Pelusi S, Aliberti S, Bosari S, Lamorte G, Ostadreza M, Carpani R, Hu C, Malvestiti F, Suardi C, Müller F, D'Amato M, Tita R, Mencarelli MA, Lo Rizzo C, Pinto AM, Illig T, Volland S, Popov A, Dei S, Krieger JE, Jannes CE, Ramos Lima I, Teruo Tada M, Velho M, Marques E, Valino K, Antinori A, Vergori A, Emiliozzi A, Rico V, Aguero D, Lluis Bedini J, Domingo C, Robles V, Soriano A, Sibila O, Castro P, Lozano F, Angelini C, Kurihara H, Ciccarelli M, Bocciolone M, Preatoni P, Omodei P, Castoldi M, CasHumanitas Gavazzeni Covid-Task Forcetoldi T, Ruiz Jaén F, Márquez L, Rusconi S, Riva A, Sanarico M, Gabbi C, Tommasi A, Paciosi F, Francisci D, Schiaroli E, Di Biagio A, Scaggiante R, Gatti F, Mussini C, Goikoetxea J, Povysil G, Bhardwaj N, Winter C, Dudman S, Lind A, Maj C, Kurth I, Eggermann T, Nöthen MM, Fazaal J, Schröder J, Blasi F, Medrano FJ, Dueñas C, Gutierrez S, Ravaglia S, Voza A, Tentorio P, Badalamenti S, Bombace S, Masetti C, Colapietro F, Solano S, Barbieri V, Humanitas Covid-Task Force T, Bussotti M, La Rovere MT, Sarzi-Braga S, Parati G, Crotti L, Squeo GM, Forgetta V, Morrison DR, Ghosh B, Laurent L, Henry D, Adra D, Abdullah T, Adeleye O, Mamlouk N, Kimchi N, Afrasiabi Z, Rezk N, Vulesevic B, Bouab M, Guzman C, Petitjean L, Tselios C, Xue X, Afilalo J, Heggelund L, Lena F, Oliveira M, Brenner B, Belisle A, Li R, Lepage P, Ragoussis J, Auld D, Lathrop GM, Mooser V, Zguro K, Furini S, Tumbarello M, Montagnani F, Della Monica M, Piscopo C, Artuso R, Perticaroli V, Doddato G, Giliberti A, Croci S, Meloni I, Beligni G, Fallerini C, Daga S, Baldassarri M, Frullanti E, Di Sarno L, Palmieri M, Carriero ML, Alaverdian D, Valentino F, Bruttini M, Rojo Rello S, Orduña A, Eiros JM, Dominguez-Gil M, Chueca N, Sanguinetti M, Masucci L, Fiz-Lopez A, Arribas E, de la Cal P, Wendtner CM, Intxausti M, Sancho C, Garrido Chercoles A, Gutiérrez-Stampa MA, España PP, Urrechaga E, Mandalà M, Giorli A, Salerni L, Conticini E, Cantarini L, Frediani B, Llucia-Carol L, Cullell N, Raimondi F, Fevang B, Goffard JC, Menatti E, Erber J, Canaccini A, Verzuri A, Anemoli V, Coviello DA, Mancarella S, Tavecchia L, Belli MA, Rizzi M, Maggiolo F, Ripamonti D, Bargagli E, Bergantini L, D'Alessandro M, Cameli P, Bennett D, Fiorentino G, Georges M, Guerrero JM, de la Horra C, Calderon E, Delgado J, Morilla R, Friaza V, Gori M, Marsal S, Rojo Rello S |
| Keywords | COVID-19, Genetic variation, Genetics |
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