Details

Autor(en) / Beteiligte

• Cruz, Raquel
• Heredia, Miguel López
• Pita, Guillermo
• Nevado, Julian
• Aguado, Jose María
• Aguilera-Albesa, Sergio
• Almadana, Virginia
• Alvarez, Nuria
• Andreu-Bernabeu, Álvaro
• Arana-Arri, Eunate
• Arango, Celso
• Arranz, María J
• Artiga, Maria-Jesus
• Baptista-Rosas, Raúl C
• Barreda-Sánchez, María
• Belhassen-Garcia, Moncef
• Bezerra, Marcos A C
• Brion, María
• Brugada, Ramón
• Bustos, Matilde
• Carbonell, Cristina
• Conde-Vicente, Rosa
• Cordero-Lorenzana, M Lourdes
• Corton, Marta
• Darnaude, M Teresa
• De Martino-Rodríguez, Alba
• Bustamante, Aranzazu Diaz
• Domínguez-Garrido, Elena
• Fernández-Rodríguez, Amanda
• Fernández-Villa, Tania
• Gil-Fournier, Belén
• Álvarez, Beatriz González
• Quirós, Fernan Gonzalez Bernaldo
• González-Peñas, Javier
• Gutiérrez-Bautista, Juan F
• Jimenez-Sousa, María A
• Borja, Anabel Liger
• Lopez-Rodriguez, Rosario
• Mancebo, Esther
• Martín-López, Caridad
• Martín, Vicente
• Martinez-Nieto, Oscar
• Martinez-Lopez, Iciar
• Martinez-Resendez, Michel F
• Mazzeu, Juliana A
• Cuerda, Victor Moreno
• Oliveira, Silviene F
• Ortega-Paino, Eva
• Paz-Artal, Estela
• Santos, Ney P C
• Pérez-Matute, Patricia
• Pérez-Tomás, M Elena
• Perucho, Teresa
• Pinsach-Abuin, Mel Lina
• Porras-Hurtado, Gloria L
• Pujol, Aurora
• Resino, Salvador
• Rodríguez-Ruiz, Emilio
• Rodriguez-Artalejo, Fernando
• Rodriguez-Garcia, José A
• Soria, José Manuel
• Souto, Juan Carlos
• Tamayo, Eduardo
• Taracido-Fernandez, Juan Carlos
• Torres-Tobar, Lilian
• Valencia-Ramos, Juan
• Zarate, Ruth
• Nakanishi, Tomoko
• Bouysran, Youssef
• Palom, Adriana
• Ellinghaus, David
• Martínez-Bueno, Manuel
• Rolker, Selina
• Fava, Francesca
• Spinner, Christoph D
• Bernardo, David
• Garcia, Federico
• Darcis, Gilles
• Fernández-Cadenas, Israel
• Holter, Jan Cato
• Banales, Jesus M
• Asselta, Rosanna
• Romero-Gómez, Manuel
• Nafría-Jiménez, Beatriz
• Hov, Johannes R
• Planas, Anna M
• Buti, Maria
• Alarcón-Riquelme, Marta E
• Schulte, Eva C
• Valenti, Luca
• Zeberg, Hugo
• Richards, Brent
• Ganna, Andrea
• Boada, Mercè
• Ruiz, Agustín
• Sánchez, Pascual
• Real, Luis Miguel
• Flores, Carlos
• Lapunzina, Pablo
• Carracedo, Ángel

Titel

Novel genes and sex differences in COVID-19 severity

Ist Teil von

• Human molecular genetics, 2022-06, Vol.31 (22), p.3789-3806

Ort / Verlag

England: Oxford University Press

Erscheinungsjahr

2022

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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.