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00925njm 22002777a 4500 dc Cruz, Raquel author Diz-de Almeida, Silvia author López Heredia, Miguel author Quintela, Inés author Ceballos, Francisco C author Pita, Guillermo author Lorenzo-Salazar, José M author González-Montelongo, Rafaela author Gago-Dominguez, Manuela author Sevilla Porras, Marta author Tenorio Castaño, Jair Antonio author Nevado, Julian author Aguado, José María author Aguilar, Carlos author Aguilera-Albesa, Sergio author Almadana, Virginia author Almoguera, Berta author Alvarez, Nuria author Andreu-Bernabeu, Álvaro author Arana-Arri, Eunate author Arango, Celso author Arranz, María J author Artiga, Maria-Jesus author Baptista-Rosas, Raúl C author Barreda-Sánchez, María author Belhassen-García, Moncef author Bezerra, Joao F author Bezerra, Marcos A C author Boix-Palop, Lucía author Brion, María author Brugada, Ramón author Bustos, Matilde author Calderón, Enrique J author Carbonell, Cristina author Castano, Luis author Castelao, Jose E author Conde-Vicente, Rosa author Cordero-Lorenzana, M Lourdes author Cortes-Sanchez, Jose L author Corton, Marta author Darnaude, M Teresa author De Martino-Rodríguez, Alba author Campo-Pérez, Victor author Diaz Bustamante, Aranzazu author Domínguez-Garrido, Elena author Luchessi, Andre D author Eirós, Rocío author Estigarribia Sanabria, Gladys Mercedes author Fariñas, María Carmen author Fernández-Robelo, Uxía author Fernandez-Rodriguez, Amanda author Fernández-Villa, Tania author Gil-Fournier, Belén author Gómez-Arrue, Javier author González Álvarez, Beatriz author Gonzalez Bernaldo Quirós, Fernan author González-Peñas, Javier author Gutiérrez-Bautista, Juan F author Herrero, María José author Herrero-Gonzalez, Antonio author Jimenez-Sousa, Maria Angeles author Lattig, María Claudia author Borja, Anabel Liger author Lopez-Rodriguez, Rosario author Mancebo, Esther author Martín-López, Caridad author Martín, Vicente author Martinez-Nieto, Oscar author Martinez-Lopez, Iciar author Martinez-Resendez, Michel F author Martinez-Perez, Angel author Mazzeu, Juliana A author Merayo Macías, Eleuterio author Minguez, Pablo author Moreno Cuerda, Victor author Silbiger, Vivian N author Oliveira, Silviene F author Ortega-Paino, Eva author Parellada, Mara author Paz-Artal, Estela author Santos, Ney PC author Pérez-Matute, Patricia author Perez, Patricia author Pérez-Tomás, M Elena author Perucho, Teresa author Pinsach-Abuin, Mel·lina author Pompa-Mera, Ericka N author Porras-Hurtado, Gloria L author Pujol, Aurora author Ramiro León, Soraya author Resino, Salvador author Fernandes, Marianne R author Rodríguez-Ruiz, Emilio author Rodríguez-Artalejo, Fernando author Rodriguez-Garcia, José A author Ruiz-Cabello, Francisco author Ruiz-Hornillos, Javier author Ryan, Pablo author Soria, José Manuel author Souto, Juan Carlos author Tamayo, Eduardo author Tamayo-Velasco, Álvaro author Taracido-Fernandez, Juan Carlos author Teper, Alejandro author Torres-Tobar, Lilian author Urioste, Miguel author Valencia-Ramos, Juan author Yáñez, Zuleima author Zarate, Ruth author Nakanishi, Tomoko author Pigazzini, Sara author Degenhardt, Frauke author Butler-Laporte, Guillaume author Maya-Miles, Douglas author Bujanda, Luis author Bouysran, Youssef author Palom, Adriana author Ellinghaus, David author Martínez-Bueno, Manuel author Rolker, Selina author Amitrano, Sara author Roade, Luisa author Fava, Francesca author Spinner, Christoph D author Prati, Daniele author Bernardo, David author García, Federico author Darcis, Gilles author Fernández-Cadenas, Israel author Holter, Jan Cato author Banales, Jesus M author Frithiof, Robert author Duga, Stefano author Asselta, Rosanna author Pereira, Alexandre C author Romero-Gómez, Manuel author Nafría-Jiménez, Beatriz author Hov, Johannes R author Migeotte, Isabelle author Renieri, Alessandra author Planas, Anna M author Ludwig, Kerstin U author Buti, Maria author Rahmouni, Souad author Alarcón-Riquelme, Marta E author Schulte, Eva C author Franke, Andre author Karlsen, Tom H author Valenti, Luca author Zeberg, Hugo author Richards, Brent author Ganna, Andrea author Boada, Mercè author Rojas, Itziar author Ruiz, Agustín author Sánchez, Pascual author Real, Luis Miguel author Guillén-Navarro, Encarna author Ayuso, Carmen author González-Neira, Anna author Riancho, José A author Rojas-Martinez, Augusto author Flores, Carlos author Lapunzina, Pablo author Carracedo, Ángel author SCOURGE Cohort Group author HOSTAGE Cohort Group author GRA@CE Cohort Group author 2022-06-16 Here we describe the results of a genome-wide study conducted in 11 939 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 < 5x10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (p = 1.3x10-22 and p = 8.1x10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (p = 4.4x10-8). 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 = 2.7x10-8) and ARHGAP33 (p = 1.3x10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, p = 4.1x10-8). 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. Hum Mol Genet. 2022 Jun 16;ddac132. 10.1093/hmg/ddac132 1460-2083 Human molecular genetics 35708486 http://hdl.handle.net/20.500.12105/15073 Novel genes and sex differences in COVID-19 severity