Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality.
Клиническое исследованиеСтатьяМногоцентровое исследованиеПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Nakanishi Tomoko, Pigazzini Sara, Degenhardt Frauke, Cordioli Mattia, Butler-Laporte Guillaume, Maya-Miles Douglas, Bujanda Luis, Bouysran Youssef, Niemi Mari Ek, Palom Adriana, Ellinghaus David, Khan Atlas, Martínez-Bueno Manuel, Rolker Selina, Amitrano Sara, Roade Tato Luisa, Fava Francesca, FinnGen, COVID-19 Host Genetics Initiative (HGI), Spinner Christoph D, Prati Daniele, Bernardo David, Garcia Federico, Darcis Gilles, Fernández-Cadenas Israel, Holter Jan Cato, Banales Jesus M, Frithiof Robert, Kiryluk Krzysztof, Duga Stefano, Asselta Rosanna, Pereira Alexandre C, Romero-Gómez Manuel, Nafría-Jiménez Beatriz, Hov Johannes R, Migeotte Isabelle, Renieri Alessandra, Planas Anna M, Ludwig Kerstin U, Buti Maria, Rahmouni Souad, Alarcón-Riquelme Marta E, Schulte Eva C, Franke Andre, Karlsen Tom H, Valenti Luca, Zeberg Hugo, Richards J Brent, Ganna Andrea
Аннотация
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.