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 Nafría-Jiménez, Beatriz
A1 Bouysran, Youssef
A1 Niemi, Mari
A1 Palom, Adriana
A1 Ellinghaus, David
A1 Khan, Atlas
A1 Martínez-Bueno, Manuel
A1 Rolker, Selina
A1 Amitano, Sara
A1 Tato, Luisa Roade
A1 FinnGen, The COVID-19 Host Genetics Initiative
A1 Fava, Francesca
A1 Spinner, Christoph D
A1 Prati, Daniele
A1 Bernardo, David
A1 Garcia, Federico
A1 Darcis, Gilles
A1 Fernández-Cadenas, Israel
A1 Holter, Jan Cato
A1 Banales, Jesus
A1 Frithiof, Robert
A1 Kiryluk, Krzysztof
A1 Duga, Stefano
A1 Asselta, Rosanna
A1 Pereira, Alexandre C
A1 Romero-Gómez, Manuel
A1 Bujanda, Luis
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 Alarcón-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
AB There is considerable variability in COVID-19 outcomes amongst younger adults-and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium. The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors. We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1·4, 95% confidence interval [CI] 1·2-1·6) and COVID-19 related mortality (HR 1·5, 95%CI 1·3-1·8). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2·0, 95%CI 1·6-2·6), venous thromboembolism (OR 1·7, 95%CI 1·2-2·4), and hepatic injury (OR 1·6, 95%CI 1·2-2·0). Risk allele carriers ≤ 60 years had higher odds of death or severe respiratory failure (OR 2·6, 95%CI 1·8-3·9) compared to those > 60 years OR 1·5 (95%CI 1·3-1·9, interaction p-value=0·04). Amongst individuals ≤ 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31·8% (95%CI 27·6-36·2) were risk variant carriers, compared to 13·9% (95%CI 12·6-15·2%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those ≤ 60 years improved when including the risk allele (AUC 0·82 vs 0·84, p=0·016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk factors. The major common COVID-19 risk locus on chromosome 3 is associated with increased risks of morbidity and mortality-and these are more pronounced amongst individuals ≤ 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management. Funding was obtained by each of the participating cohorts individually.
YR 2021
FD 2021-03-12
LK https://hdl.handle.net/10668/25276
UL https://hdl.handle.net/10668/25276
LA en
DS RISalud
RD Apr 5, 2025