RT Journal Article
T1 Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality
A1 Nakanishi, Tomoko
A1 Pigazzini, Sara
A1 Degenhardt, Frauke
A1 Cordioli, Mattia
A1 Butler-Laporte, Guillaume
A1 Maya-Miles, Douglas
A1 Bujanda, Luis
A1 Bouysran, Youssef
A1 Niemi, Mari E. K.
A1 Palom, Adriana
A1 Ellinghaus, David
A1 Khan, Atlas
A1 Martinez-Bueno, Manuel
A1 Rolker, Selina
A1 Amitrano, Sara
A1 Roade Tato, Luisa
A1 Fava, Francesca
A1 Spinner, Christoph D.
A1 Prati, Daniele
A1 Bernardo, David
A1 Garcia, Federico
A1 Darcis, Gilles
A1 Fernandez-Cadenas, Israel
A1 Holter, Jan Cato
A1 Banales, Jesus M.
A1 Frithiof, Robert
A1 Kiryluk, Krzysztof
A1 Duga, Stefano
A1 Asselta, Rosanna
A1 Pereira, Alexandre C.
A1 Romero-Gomez, Manuel
A1 Nafria-Jimenez, Beatriz
A1 Hov, Johannes R.
A1 Migeotte, Isabelle
A1 Renieri, Alessandra
A1 Planas, Anna M.
A1 Ludwig, Kerstin U.
A1 Buti, Maria
A1 Rahmouni, Souad
A1 Alarcon-Riquelme, Marta E.
A1 Schulte, Eva C.
A1 Franke, Andre
A1 Karlsen, Tom H.
A1 Valenti, Luca
A1 Zeberg, Hugo
A1 Richards, J. Brent
A1 Ganna, Andrea
A1 FinnGen, 
A1 COVID-19 Host Genetics Initiative, 
K1 Vaccine
AB 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.
PB Amer soc clinical investigation inc
SN 0021-9738
YR 2021
FD 2021-12-01
LK https://hdl.handle.net/10668/25997
UL https://hdl.handle.net/10668/25997
LA en
DS RISalud
RD Apr 8, 2025