Produção Nacional
Revisado por pares
Novel genes and sex differences in COVID-19 severity
2022; Oxford University Press; Volume: 31; Issue: 22 Linguagem: Inglês
10.1093/hmg/ddac132
ISSN1460-2083
AutoresRaquel Cruz, Silvia Diz‐de Almeida, Miguel López de Heredia, Inés Quintela, Francisco C. Ceballos, Guillermo Pita, José M. Lorenzo-Salazar, Rafaela González‐Montelongo, Manuela Gago‐Dominguez, Marta Sevilla Porras, Jair Tenorio, Julián Nevado, José María Aguado, Carlos Aguilar, Sergio Aguilera, Virginia Almadana Pacheco, Berta Almoguera, Núria Álvarez, Álvaro Andreu-Bernabeu, Eunate Arana‐Arri, Celso Arango, María J. Arranz, María-Jesús Artiga, Raúl C. Baptista‐Rosas, María Barreda‐Sánchez, Moncef Belhassen‐García, Joao F. Bezerra, Marcos Bezerra, Lucía Boix-Palop, Marı́a Brión, Ramón Brugada, Matilde Bustos, Enrique J. Calderón, Cristina Carbonell, Luís Castaño, Jose E. Castelao, R. Conde, M. Lourdes Cordero-Lorenzana, José Luis Cortés-Sánchez, Marta Cortón, M. Teresa Darnaude, Alba De Martino, Víctor del Campo-Pérez, Aránzazu Díaz de Bustamante, Elena Domínguez-Garrido, André Ducati Luchessi, Rocío Eirós, Gladys Mercedes Estigarribia Sanabria, María Carmen Fariñas, Uxía Fernández-Robelo, Amanda Fernández‐Rodríguez, Tania Fernández‐Villa, Belén Gil-Fournier, Javier Gómez-Arrue, Beatriz González Álvarez, Fernán Gónzalez Bernaldo de Quirós, Javier González‐Peñas, Juan Francisco Gutiérrez‐Bautista, María José Herrero, Antonio Herrero, María A. Jiménez‐Sousa, María Claudia Lattig, Anabel Liger Borja, Rosario López‐Rodríguez, Esther Mancebo, Caridad Martín-López, Vicente Martín, Óscar Martínez-Nieto, Iciar Martínez‐López, Michel F. Martínez‐Reséndez, Ángel Martínez-Pérez, Juliana F. Mazzeu, Eleuterio Merayo Macías, Pablo Mínguez, Víctor Moreno Cuerda, Vivian Nogueira Silbiger, Silviene Fabiana de Oliveira, Eva Ortega‐Paino, Mara Parellada, Estela Paz‐Artal, Ney P. C. Santos, Patricia Pérez‐Matute, Patricia Perez, M. Elena Pérez-Tomás, Teresa Perucho, Mel·lina Pinsach‐Abuin, Ericka N. Pompa‐Mera, Gloria Liliana Porras-Hurtado, Aurora Pujol, Soraya Ramiro León, Salvador Resino, Marianne Rodrigues Fernandes, Emilio Rodríguez‐Ruiz, Fernando Rodríguez‐Artalejo, José A Rodriguez-Garcia, Francisco Ruiz Cabello, Javier Ruiz‐Hornillos, Pablo Ryan, José Manuel Soria, Juan Carlos Souto, Eduardo Tamayo, Álvaro Tamayo-Velasco, Juan Carlos Taracido‐Fernández, Alejandro Teper, Lilian Torres-Tobar, Miguel Urioste, Juan Valencia-Ramos, Zuleima Yáñez, Ruth Zárate, Tomoko Nakanishi, Sara Pigazzini, Frauke Degenhardt, Guillaume Butler‐Laporte, Douglas Maya‐Miles, Luís Bujanda, Youssef Bouysran, Adriana Palom, David Ellinghaus, Manuel Martínez‐Bueno, Selina Rolker, Sara Amitrano, Luisa Roade, Francesca Fava, Christoph D. Spinner, Daniele Prati, David Bernardo, Féderico García, Gilles Darcis, Israel Fernández‐Cadenas, Jan Cato Holter, Jesús M. Bañales, Robert Frithiof, Stefano Duga, Rosanna Asselta, Alexandre C. Pereira, Manuel Romero‐Gómez, Beatriz Nafría-Jiménez, Johannes R. Hov, Isabelle Migeotte, Alessandra Renieri, Anna M. Planas, Kerstin U. Ludwig, Marı́a Buti, Souad Rahmouni, Marta E. Alarcón‐Riquelme, Eva C. Schulte, André Franke, Tom H. Karlsen, Luca Valenti, Hugo Zeberg, Brent Richards, Andrea Ganna, Merçé Boada, Itziar de Rojas, Agustı́n Ruiz, Pascual Sánchez‐Juan, Luís Miguel Real, Encarna Guillén‐Navarro, Carmen Ayuso, Anna González‐Neira, José A. Riancho, Augusto Rojas‐Martínez, Carlos Flores, Pablo Lapunzina, Ãngel Carracedo,
Tópico(s)PARP inhibition in cancer therapy
ResumoHere, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10-22 and P = 8.1 × 10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10-8) and ARHGAP33 (P = 1.3 × 10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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