| Title | Novel genes and sex differences in COVID-19 severity. |
| Publication Type | Journal Article |
| Year of Publication | 2022 |
| Authors | Cruz, R, de Almeida, SDiz-, Heredia, MLópez, Quintela, I, Ceballos, FC, Pita, G, Lorenzo-Salazar, JM, González-Montelongo, R, Gago-Domínguez, M, Porras, MSevilla, Castaño, JAntonio Te, Nevado, J, Aguado, JMaría, Aguilar, C, Aguilera-Albesa, S, Almadana, V, Almoguera, B, Alvarez, N, Andreu-Bernabeu, Á, Arana-Arri, E, Arango, C, Arranz, MJ, Artiga, M-J, Baptista-Rosas, RC, Barreda-Sánchez, M, Belhassen-Garcia, M, Bezerra, JF, Bezerra, MAC, Boix-Palop, L, Brión, M, Brugada, R, Bustos, M, Calderón, EJ, Carbonell, C, Castano, L, Castelao, JE, Conde-Vicente, R, M Cordero-Lorenzana, L, Cortes-Sanchez, JL, Corton, M, M Darnaude, T, De Martino-Rodríguez, A, Campo-Pérez, V, Bustamante, ADiaz, Domínguez-Garrido, E, Luchessi, AD, Eirós, R, Sanabria, GMercedes E, Fariñas, MCarmen, Fernández-Robelo, U, Fernández-Rodríguez, A, Fernández-Villa, T, Gil-Fournier, B, Gómez-Arrue, J, Álvarez, BGonzález, Quirós, FGonzalez B, González-Peñas, J, Gutiérrez-Bautista, JF, Herrero, MJosé, Herrero-Gonzalez, A, Jimenez-Sousa, MA, Lattig, MClaudia, Borja, ALiger, Lopez-Rodriguez, R, Mancebo, E, Martín-López, C, Martín, V, Martinez-Nieto, O, Martinez-Lopez, I, Martinez-Resendez, MF, Martinez-Perez, Á, Mazzeu, JA, Macías, EMerayo, Minguez, P, Cuerda, VMoreno, Silbiger, VN, Oliveira, SF, Ortega-Paino, E, Parellada, M, Paz-Artal, E, Santos, NPC, Pérez-Matute, P, Perez, P, M Pérez-Tomás, E, Perucho, T, Pinsach-Abuin, MLina, Pompa-Mera, EN, Porras-Hurtado, GL, Pujol, A, León, SRamiro, Resino, S, Fernandes, MR, Rodríguez-Ruiz, E, Rodriguez-Artalejo, F, Rodriguez-Garcia, JA, Ruiz-Cabello, F, Ruiz-Hornillos, J, Ryan, P, Soria, JManuel, Souto, JCarlos, Tamayo, E, Tamayo-Velasco, A, Taracido-Fernandez, JCarlos, Teper, A, Torres-Tobar, L, Urioste, M, Valencia-Ramos, J, Yáñez, Z, Zarate, R, Nakanishi, T, Pigazzini, S, Degenhardt, F, Butler-Laporte, G, Maya-Miles, D, Bujanda, L, Bouysran, Y, Palom, A, Ellinghaus, D, Martínez-Bueno, M, Rolker, S, Amitrano, S, Roade, L, Fava, F, Spinner, CD, Prati, D, Bernardo, D, García, F, Darcis, G, Fernández-Cadenas, I, Holter, JCato, Banales, JM, Frithiof, R, Duga, S, Asselta, R, Pereira, AC, Romero-Gómez, M, Nafría-Jiménez, B, Hov, JR, Migeotte, I, Renieri, A, Planas, AM, Ludwig, KU, Buti, M, Rahmouni, S, Alarcón-Riquelme, ME, Schulte, EC, Franke, A, Karlsen, TH, Valenti, L, Zeberg, H, Richards, B, Ganna, A, Boada, M, Rojas, I, Ruiz, A, Sánchez, P, Real, LMiguel, Guillén-Navarro, E, Ayuso, C, González-Neira, A, Riancho, JA, Rojas-Martinez, A, Flores, C, Lapunzina, P, Carracedo, Á |
| Corporate Authors | SCOURGE Cohort Group, HOSTAGE Cohort Group, GRA@CE Cohort Group |
| Journal | Hum Mol Genet |
| Date Published | 2022 Jun 16 |
| ISSN | 1460-2083 |
| Abstract | 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. |
| DOI | 10.1093/hmg/ddac132 |
| Alternate Journal | Hum Mol Genet |
| PubMed ID | 35708486 |
