% pubman genre = article @article{item_3358377, title = {{Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality}}, author = {Nakanishi, Tomoko and Pigazzini, Sara and Degenhardt, Frauke and Cordioli, Mattia and Butler-Laporte, Guillaume and Maya-Miles, Douglas and Bujanda, Luis and Bouysran, Youssef and Niemi, Mari E.K. and Palom, Adriana and Ellinghaus, David and Khan, Atlas and Mart{\'\i}nez-Bueno, Manuel and Rolker, Selina and Amitrano, Sara and Tato, Luisa Roade and Fava, Francesca and FinnGen, and (HGI), The COVID-19 Host Genetics Initiative and Spinner, Christoph D. and Prati, Daniele and Bernardo, David and Garcia, Federico and Darcis, Gilles and Fern{\'a}ndez-Cadenas, Israel and Holter, Jan Cato and Banales, Jesus M. and Frithiof, Robert and Kiryluk, Krzysztof and Duga, Stefano and Asselta, Rosanna and Pereira, Alexandre C. and Romero-G{\'o}mez, Manuel and Nafr{\'\i}a-Jim{\'e}nez, Beatriz and Hov, Johannes R. and Migeotte, Isabelle and Renieri, Alessandra and Planas, Anna M. and Ludwig, Kerstin U. and Buti, Maria and Rahmouni, Souad and Alarc{\'o}n-Riquelme, Marta E. and Schulte, Eva C. and Franke, Andre and Karlsen, Tom H. and Valenti, Luca and Zeberg, Hugo and Richards, J. Brent and Ganna, Andrea}, language = {eng}, issn = {0021-9738}, doi = {10.1172/JCI152386}, publisher = {American Society for Clinical Investigation}, address = {New York, NY}, year = {2021}, date = {2021-12-01}, abstract = {{There is considerable variability in COVID-19 outcomes among younger adults, and some of this variation may be due to genetic predisposition.{\textless}br{\textgreater}We combined individual level data from 13,888 COVID-19 patients (n {\textequals} 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.{\textless}br{\textgreater}We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (HR, 1.4; 95 CI, 1.2{\textendash}1.7). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (OR, 2.1; 95 CI, 1.6{\textendash}2.6), venous thromboembolism (OR, 1.7; 95 CI, 1.2{\textendash}2.4), and hepatic injury (OR, 1.5; 95 CI, 1.2{\textendash}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{\textendash}3.9) compared with those of more than 60 years (OR, 1.5; 95 CI, 1.2{\textendash}1.8; interaction, P {\textequals} 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.{\textless}br{\textgreater}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.}}, journal = {{The Journal of Clinical Investigation}}, volume = {131}, number = {23}, }