Novel genes and sex differences in COVID-19 severity


Por: Cruz, R, Diz-de Almeida, S, de Heredia, ML, Quintela, I, Ceballos, FC, Lorenzo-Salazar, GM, Gonzalez-Montelongo, R, Gago-Dominguez, M, Porras, MS, Castano, JAT, Nevado, J, Aguado, JM, Aguilar, C, Aguilera-Albesa, S, Almadana, V, Almoguera, B, Alvarez, N, Andreu-Bernabeu, A, Arana-Arri, E, Arango, C, Arranz, MJ, Artiga, MJ, Baptista-Rosas, RC, Barreda-Sanchez, M, Belhassen-Garcia, M, Bezerra, JF, Bezerra, MAC, Boix-Palop, L, Brion, M, Brugada, R, Bustos, M, Calderon, EJ, Carbonell, C, Castano, L, Castelao, JE, Conde-Vicente, R, Cordero-Lorenzana, ML, Cortes-Sanchez, JL, Corton, M, Darnaude, MT, De Martino-Rodriguez, A, del Campo-Perez, V, de Bustamante, AD, Dominguez-Garrido, E, Luchessi, AD, Eiros, R, Sanabria, GME, Carmen Farinas, M, Fernandez-Robelo, U, Fernandez-Rodriguez, A, Fernandez-Villa, T, Gil-Fournier, B, Gomez-Arrue, J, Alvarez, BG, de Quiros, FGB, Gonzalez-Penas, J, Gutierrez-Bautista, JF, Herrero, MJ, Herrero-Gonzalez, A, Jimenez-Sousa, MA, Lattig, MC, Borja, AL, Lopez-Rodriguez, R, Mancebo, E, Martin-Lopez, C, Martin, V, Martinez-Nieto, O, Martinez-Lopez, I, Martinez-Resendez, MF, Martinez-Perez, A, Mazzeu, JF, Macias, EM, Minguez, P, Cuerda, VM, Silbiger, VN, Oliveira, SF, Ortega-Paino, E, Parellada, M, Paz-Artal, E, Santos, NPC, Perez-Matute, P, Perez, P, Perez-Tomas, ME, Perucho, T, Pinsach-Abuin, ML, Pompa-Mera, EN, Porras-Hurtado, GL, Pujol, A, Leon, SR, Resino, S, Fernandes, MR, Rodriguez-Ruiz, E, Rodriguez-Artalejo, F, Rodriguez-Garcia, JA, Cabello, FR, Ruiz-Hornillos, J, Ryan, P, Soria, JM, Souto, JC, Tamayo, E, Tamayo-Velasco, A, Taracido-Fernandez, JC, Teper, A, Torres-Tobar, L, Urioste, M, Valencia-Ramos, J, Yanez, Z, Zarate, R, Nakanishi, T, Pigazzini, S, Degenhardt, F, Butler-Laporte, G, Maya-Miles, D, Bujanda, L, Bouysran, Y, Palom, A, Ellinghaus, D, Martinez-Bueno, M, Rolker, S, Amitrano, S, Roade, L, Fava, F, Spinner, CD, Prati, D, Bernardo, D, Garcia, F, Darcis, G, Fernandez-Cadenas, I, Holter, JC, Banales, JM, Frithiof, R, Duga, S, Asselta, R, Pereira, AC, Romero-Gomez, M, Nafria-Jimenez, B, Hov, JR, Migeotte, I, Renieri, A, Planas, AM, Ludwig, KU, Buti, M, Rahmouni, S, Alarcon-Riquelme, ME, Schulte, EC, Franke, A, Karlsen, TH, Valenti, L, Zeberg, H, Richards, B, Ganna, A, Boada, M, de Rojas, I, Ruiz, A, Sanchez-Juan, P, Real, LM, Guillen-Navarro, E, Ayuso, C, Gonzalez-Neira, A, Riancho, JA, Rojas-Martinez, A, Flores, C, Lapunzina, P, Carracedo, A

Publicada: 15 nov 2022 Ahead of Print: 1 jun 2022
Resumen:
Here, we describe the results of a genome-wide study conducted in 11939 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<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 (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=4.1x10(-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.

Filiaciones:
Cruz, R:
 Univ Santiago de Compostela, Ctr Nacl Genotipado CEGEN, Santiago De Compostela 15706, Spain

 Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid 28029, Spain

 Inst Invest Sanitaria Santiago IDIS, Santiago De Compostela 15706, Spain

 Univ Santiago de Compostela, Ctr Singular Invest Med Mol & Enfermedades Cronic, Santiago De Compostela 15782, Spain

Diz-de Almeida, S:
 Univ Santiago de Compostela, Ctr Singular Invest Med Mol & Enfermedades Cronic, Santiago De Compostela 15782, Spain

de Heredia, ML:
 Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid 28029, Spain

Quintela, I:
 Univ Santiago de Compostela, Ctr Nacl Genotipado CEGEN, Santiago De Compostela 15706, Spain

Ceballos, FC:
 Inst Salud Carlos III ISCIII, Ctr Nacl Microbiol CNM, Unidad Infecc Viral & Inmun, Madrid 28220, Spain

Lorenzo-Salazar, GM:
 Inst Tecnol & Energias Renovables, Genom Div, Santa Cruz De Tenerife 38600, Spain

Gonzalez-Montelongo, R:
 Inst Tecnol & Energias Renovables, Genom Div, Santa Cruz De Tenerife 38600, Spain

Gago-Dominguez, M:
 Inst Invest Sanitaria Santiago IDIS, Santiago De Compostela 15706, Spain

 Fdn Publ Galegade Med Xenom, Sistema Galegode Saude SERGAS, Santiago De Compostela 15706, Spain

Porras, MS:
 Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid 28029, Spain

 Hosp Univ La Paz IDIPAZ, Inst Genet Med & Mol INGEMM, Madrid 28046, Spain

Castano, JAT:
 Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid 28029, Spain

 Hosp Univ La Paz IDIPAZ, Inst Genet Med & Mol INGEMM, Madrid 28046, Spain

 ERN, ITHACA, European Reference Network, Amsterdam, Netherlands

Nevado, J:
 Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid 28029, Spain

 Hosp Univ La Paz IDIPAZ, Inst Genet Med & Mol INGEMM, Madrid 28046, Spain

 ERN, ITHACA, European Reference Network, Amsterdam, Netherlands

Aguado, JM:
 Hosp Univ 12 Octubre, Inst Invest Sanitaria Hosp 12 Octubre imas12, Unit Infect Dis, Madrid 28041, Spain

 Inst Salud Carlos III, Spanish Network Res Infect Dis REIPI RD16 0016 00, Madrid 28029, Spain

 Univ Complutense, Sch Med, Madrid 28040, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Infecciosas CI, Madrid 28029, Spain

Aguilar, C:
 Hosp Gen Santa Barbara Soria, Soria 42005, Spain

Aguilera-Albesa, S:
 Navarra Hlth Serv Hosp, Dept Pediat, Pediat Neurol Unit, Pamplona 31008, Spain

 NavarraBioMed Res Grp, Navarra Hlth Serv, Pamplona 31008, Spain

Almadana, V:
 Hosp Univ Virgen Macarena, Neumol, Seville 41009, Spain

Almoguera, B:
 Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid 28029, Spain

 Univ Autonoma Madrid, Fdn Jimenez Diaz Univ Hosp, Inst Invest Sanitaria, UAM,FJD,IIS,Dept Genet & Genom, Madrid 28040, Spain

Alvarez, N:
 Spanish Natl Canc Res Ctr, Human Genotyping CEGEN Unit, Madrid 28029, Spain

Andreu-Bernabeu, A:
 Univ Complutense, Sch Med, Madrid 28040, Spain

 Hosp Gen Univ Gregorio Maranon IiSGM, Inst Psychiat & Mental Hlth, Dept Child & Adolescent Psychiat, Madrid 28007, Spain

Arana-Arri, E:
 Biocruces Bizkai HRI, Baracaldo 48903, Bizkaia, Spain

 Cruces Univ Hosp, Osakidetza, Baracaldo 48903, Bizkaia, Spain

Arango, C:
 Univ Complutense, Sch Med, Madrid 28040, Spain

 Hosp Gen Univ Gregorio Maranon IiSGM, Inst Psychiat & Mental Hlth, Dept Child & Adolescent Psychiat, Madrid 28007, Spain

 Inst Salud Carlos III, Ctr Biomed Network Res Mental Hlth CIBERSAM, Madrid 28029, Spain

Arranz, MJ:
 Fdn Docencia I Recerca Mutua Terrassa, Terrassa 08221, Spain

Artiga, MJ:
 Spanish Natl Canc Res Ctr, CNIO Biobank, Madrid 28029, Spain

Baptista-Rosas, RC:
 Hosp Gen Occidente Seguro Social, Zapopan 45170, Jalisco, Mexico

 Univ Guadalajara, Ctr Univ Tonala, Tonala 45425, Jalisco, Mexico

 Univ Guadalajara, Ctr Invest Multidisciplinario Salud, Tonala 45425, Jalisco, Mexico

Barreda-Sanchez, M:
 Inst Murciano Invest Biosanitaria IMIB Arrixaca, Murcia, Spain

 Univ Catolica San Antonio Murcia UCAM, Murcia 30120, Spain

Belhassen-Garcia, M:
 Hosp Univ Salamanca IBSAL, Serv Med Interna, Unidad Enfermedades Infecciosas, Salamanca 37007, Spain

 Univ Salamanca, Salamanca 37007, Spain

Bezerra, JF:
 Escola Tecn Saude, Lab Vigilancia Mol Aplicada, BR-68515000 Brasilia, Para, Brazil

Bezerra, MAC:
 Univ Fed Pernambuco, Genet Postgrad Program, BR-50670907 Recife, PE, Brazil

Boix-Palop, L:
 Hosp Univ Mutua Terrassa, Terrassa 08221, Spain

Brion, M:
 Inst Invest Sanitaria Santiago IDIS, Xenet Cardiovasc, Santiago De Compostela 15706, Spain

 Inst Salud Carlos III, Ctr Biomed Network Res Cardiovasc Dis CIBERCV, Madrid 28029, Spain

Brugada, R:
 Inst Salud Carlos III, Ctr Biomed Network Res Cardiovasc Dis CIBERCV, Madrid 28029, Spain

 Inst Invest Biomed Girona IDIBGI, Cardiovasc Genet Ctr, Girona 17190, Spain

 Univ Girona, Sch Med, Med Sci Dept, Girona 17190, Spain

 Hosp Josep Trueta, Cardiol Serv, Girona 17190, Spain

Bustos, M:
 Univ Seville, Virgen Rocio Univ Hosp, Consejo Super Invest Cient CSIC, Inst Biomed Seville IBiS, Seville 41013, Spain

Calderon, EJ:
 Univ Seville, Hosp Univ Virgen Rocio, Dept Med, Seville 41013, Spain

 Inst Salud Carlos III, Ctr Biomed Network Res Epidemiol & Publ Hlth CIBE, Madrid 28029, Spain

 Inst Biomed Sevilla, Seville 41013, Spain

Carbonell, C:
 Univ Salamanca, Salamanca 37007, Spain

 Hosp Univ Salamanca IBSAL, Serv Med Interna, Salamanca 37007, Spain

Castano, L:
 Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid 28029, Spain

 Biocruces Bizkai HRI, Baracaldo 48903, Bizkaia, Spain

 Cruces Univ Hosp, Osakidetza, Baracaldo 48903, Bizkaia, Spain

 Inst Salud Carlos III, Ctr Biomed Network Res Diabet & Metab Associated, Madrid 28029, Spain

 Univ Basque Country, UPV EHU, Bizkaia 48903, Spain

Castelao, JE:
 Inst Invest Sanitaria Galicia Sur, Xerencia Xest Integrada Vigo Serv Galego Saude, Oncol & Genet Unit, Vigo 36312, Spain

Conde-Vicente, R:
 Hosp Univ Rio Hortega, Valladolid 47012, Spain

Cordero-Lorenzana, ML:
 Complejo Hosp Univ A Coruna CHUAC, Sistema Galego Saude SERGAS, Serv Med Intens, La Coruna 15009, Spain

Cortes-Sanchez, JL:
 Tecnol Monterrey, Monterrey 64718, Mexico

 Otto Von Guericke Univ, Dept Micrograv & Translat Regenerat Med, D-39106 Magdeburg, Germany

Corton, M:
 Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid 28029, Spain

 Univ Autonoma Madrid, Fdn Jimenez Diaz Univ Hosp, Inst Invest Sanitaria, UAM,FJD,IIS,Dept Genet & Genom, Madrid 28040, Spain

Darnaude, MT:
 Hosp Univ Mostoles, Unidad Genet, Madrid 28935, Spain

De Martino-Rodriguez, A:
 Inst Aragones Ciencias Salud IACS, Zaragoza 50009, Spain

 Inst Invest Sanitaria Aragon IIS Aragon, Zaragoza 50009, Spain

del Campo-Perez, V:
 Inst Invest Sanitaria Galicia Sur, Xerencia Xest Integrada Vigo Serv Galego Saude, Prevent Med Dept, Vigo 36312, Spain

de Bustamante, AD:
 Hosp Univ Mostoles, Unidad Genet, Madrid 28935, Spain

Dominguez-Garrido, E:
 Fdn Rioja Salud, Unidad Diagnost Mol, La Rioja 26006, Spain

Luchessi, AD:
 Univ Fed Rio Grande do Norte, Dept Anal Clin & Toxicol, BR-59012570 Natal, RN, Brazil

Eiros, R:
 Hosp Univ Salamanca IBSAL, Serv Cardiol, Salamanca 37007, Spain

Sanabria, GME:
 Univ Nacl Caaguazu, Inst Reg Invest Salud, HH36 J3Q, Caaguazu, Paraguay

Carmen Farinas, M:
 IDIVAL, Cantabria 39008, Spain

 Univ Cantabria, Cantabria 39008, Spain

 Hosp UM Valdecilla, Cantabria 39008, Spain

Fernandez-Robelo, U:
 Complejo Hosp Univ A Coruna CHUAC, Urgencias Hosp, Sistema Galego Saude SERGAS, La Coruna 15009, Spain

Fernandez-Rodriguez, A:
 Inst Salud Carlos III ISCIII, Ctr Nacl Microbiol CNM, Unidad Infecc Viral & Inmun, Madrid 28220, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Infecciosas CI, Madrid 28029, Spain

Fernandez-Villa, T:
 Univ Leon, Inst Biomed IBIOMED, Grp Invest Interacc Gen Ambiente & Salud GIIGAS, Leon 24071, Spain

Gil-Fournier, B:
 Hosp Univ Getafe, Serv Genet, Madrid 28905, Spain

Gomez-Arrue, J:
 Inst Aragones Ciencias Salud IACS, Zaragoza 50009, Spain

 Inst Invest Sanitaria Aragon IIS Aragon, Zaragoza 50009, Spain

Alvarez, BG:
 Inst Aragones Ciencias Salud IACS, Zaragoza 50009, Spain

 Inst Invest Sanitaria Aragon IIS Aragon, Zaragoza 50009, Spain

de Quiros, FGB:
 Minist Salud Ciudad Buenos Aires, C1425EFD, Buenos Aires, DF, Argentina

Gonzalez-Penas, J:
 Univ Complutense, Sch Med, Madrid 28040, Spain

 Hosp Gen Univ Gregorio Maranon IiSGM, Inst Psychiat & Mental Hlth, Dept Child & Adolescent Psychiat, Madrid 28007, Spain

 Inst Salud Carlos III, Ctr Biomed Network Res Mental Hlth CIBERSAM, Madrid 28029, Spain

Gutierrez-Bautista, JF:
 Hosp Univ Virgen Nieves, Serv Anal Clin & Inmunol, Granada 18014, Spain

Herrero, MJ:
 IIS La Fe, Plataforma Farmacogenet, Valencia 46026, Spain

 Univ Valencia, Dept Farmacol, Valencia 4610, Spain

Herrero-Gonzalez, A:
 Univ Autonoma Madrid, Fdn Jimenez Diaz Univ Hosp, Inst Invest Sanitaria, UAM,FJD,IIS,Data Anal Dept, Madrid 28040, Spain

Jimenez-Sousa, MA:
 Inst Salud Carlos III ISCIII, Ctr Nacl Microbiol CNM, Unidad Infecc Viral & Inmun, Madrid 28220, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Infecciosas CI, Madrid 28029, Spain

Lattig, MC:
 Univ Los Andes, Fac Ciencias, Bogota 111711, Colombia

 SIGEN Alianza Univ Los Andes, Fdn Santa Fe Bogota, Bogota 111711, Colombia

Borja, AL:
 Hosp Gen Segovia, Med Intens, Segovia 40002, Spain

Lopez-Rodriguez, R:
 Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid 28029, Spain

 Univ Autonoma Madrid, Fdn Jimenez Diaz Univ Hosp, Inst Invest Sanitaria, UAM,FJD,IIS,Dept Genet & Genom, Madrid 28040, Spain

Mancebo, E:
 Hosp Univ 12 Octubre, Dept Immunol, Madrid 28041, Spain

 Inst Invest Sanitaria Hosp 12 Octubre imas12, Transplant Immunol & Immunodeficiencies Grp, Madrid 28041, Spain

Martin-Lopez, C:
 Hosp Gen Segovia, Med Intens, Segovia 40002, Spain

Martin, V:
 Inst Salud Carlos III, Ctr Biomed Network Res Epidemiol & Publ Hlth CIBE, Madrid 28029, Spain

 Univ Leon, Inst Biomed IBIOMED, Leon 24071, Spain

Martinez-Nieto, O:
 SIGEN Alianza Univ Los Andes, Fdn Santa Fe Bogota, Bogota 111711, Colombia

 Fdn Santa Fe Bogota, Dept Pathol & Labs, Bogota 111711, Colombia

Martinez-Lopez, I:
 Unidad Genet & Genom Islas Baleares, Islas Baleares 07120, Spain

 Hosp Univ Son Espases, Unidad Diagnost Mol & Genet Clin, Islas Baleares 07120, Spain

Martinez-Resendez, MF:
 Tecnol Monterrey, Monterrey 64718, Mexico

Martinez-Perez, A:
 Hosp Santa Creu & Sant Pau, Res Inst, IIB St Pau, Genom Complex Dis Unit, Barcelona 08041, Spain

Mazzeu, JF:
 Univ Brasilia, Fac Med, BR-70910900 Brasilia, DF, Brazil

 Univ Brasilia, Programa Pos Grad Ciencias Med, BR-70910900 Brasilia, DF, Brazil

 Univ Brasilia, Programa Pos Grad Ciencias Saude, BR-70910900 Brasilia, DF, Brazil

Macias, EM:
 Hosp El Bierzo, Unidad Cuidados Intens, Leon 24404, Spain

Minguez, P:
 Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid 28029, Spain

 Univ Autonoma Madrid, Fdn Jimenez Diaz Univ Hosp, Inst Invest Sanitaria, UAM,FJD,IIS,Dept Genet & Genom, Madrid 28040, Spain

Cuerda, VM:
 Hosp Univ Mostoles, Med Interna, Madrid 28935, Spain

 Univ Francisco Vitoria, Madrid 28223, Spain

Silbiger, VN:
 Univ Fed Rio Grande do Norte, Dept Anal Clin & Toxicol, BR-59012570 Natal, RN, Brazil

Oliveira, SF:
 Univ Brasilia, Fac Med, BR-70910900 Brasilia, DF, Brazil

 Univ Brasilia, Programa Pos Grad Ciencias Med, BR-70910900 Brasilia, DF, Brazil

 Univ Brasilia, Programa Pos Grad Biol Anim, BR-70910900 Brasilia, DF, Brazil

 Univ Brasilia, Programa Pos Grad Profiss Ensino Biol, BR-70910900 Brasilia, DF, Brazil

 Univ Brasilia, Programa Pos Grad Profiss Ensino Biol UnB, BR-70910900 Brasilia, DF, Brazil

Ortega-Paino, E:
 Spanish Natl Canc Res Ctr, CNIO Biobank, Madrid 28029, Spain

Parellada, M:
 Univ Complutense, Sch Med, Madrid 28040, Spain

 Hosp Gen Univ Gregorio Maranon IiSGM, Inst Psychiat & Mental Hlth, Dept Child & Adolescent Psychiat, Madrid 28007, Spain

 Inst Salud Carlos III, Ctr Biomed Network Res Mental Hlth CIBERSAM, Madrid 28029, Spain

Paz-Artal, E:
 Hosp Univ 12 Octubre, Dept Immunol, Madrid 28041, Spain

 Inst Invest Sanitaria Hosp 12 Octubre imas12, Transplant Immunol & Immunodeficiencies Grp, Madrid 28041, Spain

 Univ Complutense Madrid, Dept Immunol Ophthalmol & ENT, Madrid 28040, Spain

Santos, NPC:
 Univ Fed Para, Nucl Pesquisas Oncol, BR-66075110 Belem, Para, Brazil

Perez-Matute, P:
 Ctr Biomed Res La Rioja CIBIR, Infect Dis Microbiota & Metab Unit, Logrono 26006, Spain

Perez, P:
 Inditex, La Coruna 15141, Spain

Perez-Tomas, ME:
 Inst Murciano Invest Biosanitaria IMIB Arrixaca, Murcia, Spain

Perucho, T:
 GENYCA, Madrid 28220, Spain

Pinsach-Abuin, ML:
 Inst Salud Carlos III, Ctr Biomed Network Res Cardiovasc Dis CIBERCV, Madrid 28029, Spain

 Inst Invest Biomed Girona IDIBGI, Cardiovasc Genet Ctr, Girona 17190, Spain

Pompa-Mera, EN:
 Ctr Med Nacl Siglo XXI, Inst Mexicano Seguro Social IMSS, Unidad Invest Med Enfermedades Infecciosas & Para, Mexico City 02990, DF, Mexico

Porras-Hurtado, GL:
 Clin Comfamiliar Risaralda, Pereira 660003, Colombia

Pujol, A:
 Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid 28029, Spain

 Bellvitge Biomed Res Inst IDIBELL, Neurometab Dis Lab, Lhospitalet De Llobregat 08908, Spain

 Catalan Inst Res & Adv Studies ICREA, Barcelona 08010, Spain

Leon, SR:
 Hosp Univ Getafe, Serv Genet, Madrid 28905, Spain

Resino, S:
 Inst Salud Carlos III ISCIII, Ctr Nacl Microbiol CNM, Unidad Infecc Viral & Inmun, Madrid 28220, Spain

 Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Infecciosas CI, Madrid 28029, Spain

Fernandes, MR:
 Univ Fed Para, Nucl Pesquisas Oncol, BR-66075110 Belem, Para, Brazil

 Hosp Ophir Loyola, Dept Ensino & Pesquisa, BR-66063240 Belem, Para, Brazil

Rodriguez-Ruiz, E:
 Inst Invest Sanitaria Santiago IDIS, Santiago De Compostela 15706, Spain

 Hosp Clin Univ Santiago CHUS, Sistema Galego Saude SERGAS, Unidad Cuidados Intens, Santiago De Compostela 15706, Spain

Rodriguez-Artalejo, F:
 Inst Salud Carlos III, Ctr Biomed Network Res Epidemiol & Publ Hlth CIBE, Madrid 28029, Spain

 Univ Autonoma Madrid, Sch Med, Dept Prevent Med & Publ Hlth, Madrid 28049, Spain

 IdiPaz Inst Invest Sanitaria Hosp Univ La Paz, Madrid 28046, Spain

 UAM, CSIC, CEI, IMDEA Food Inst, Madrid 28049, Spain

Rodriguez-Garcia, JA:
 Complejo Asistencial Univ Leon, Leon 24071, Spain

Cabello, FR:
 Hosp Univ Virgen Nieves, Serv Anal Clin & Inmunol, Granada 18014, Spain

 Inst Invest Biosanitaria Granada ibs Granada, Granada 18012, Spain

 Univ Granada, Dept Bioquim Biol Mol & Inmunol 3, Granada 18071, Spain

Ruiz-Hornillos, J:
 Hosp Infanta Elena, Allergy Unit, Madrid 28342, Spain

 Univ Autonoma Madrid, Fdn Jimenez Diaz Univ Hosp, Inst Invest Sanitaria, UAM,FJD,IIS, Madrid 28040, Spain

 Univ Francisco Vitoria, Fac Med, Madrid 28223, Spain

Ryan, P:
 Hosp Univ Infanta Leonor, Madrid 28031, Spain

 Univ Complutense Madrid, Madrid 28040, Spain

 Gregorio Maranon Hlth Res Inst IiSGM, Madrid 28007, Spain

Soria, JM:
 Hosp Santa Creu & Sant Pau, Res Inst, IIB St Pau, Genom Complex Dis Unit, Barcelona 08041, Spain

Souto, JC:
 Hosp Santa Creu & Sant Pau, IIB St Pau, Haemostasis & Thrombosis Unit, Barcelona 08041, Spain

Tamayo, E:
 Hosp Clin Univ Valladolid, Serv Anestesiol & Reanimac, Valladolid 47003, Spain

 Univ Valladolid, Dept Cirugia, Valladolid 47005, Spain

Tamayo-Velasco, A:
 Hosp Clin Univ Valladolid, Serv Hematol & Hemoterapia, Valladolid 47003, Spain

Taracido-Fernandez, JC:
 Univ Autonoma Madrid, Fdn Jimenez Diaz Univ Hosp, Inst Invest Sanitaria, UAM,FJD,IIS,Data Anal Dept, Madrid 28040, Spain

Teper, A:
 Hosp Ninos Dr Ricardo Gutierrez, C1425EFD, Buenos Aires, DF, Argentina

Torres-Tobar, L:
 Fdn Univ Ciencias Salud, Bogota 113827, Colombia

Urioste, M:
 Spanish Natl Canc Res Ctr, Familial Canc Clin Unit, Madrid 28029, Spain

Valencia-Ramos, J:
 Univ Hosp Burgos, Burgos 09006, Spain

Yanez, Z:
 Univ Simon Bolivar, Fac Ciencias Salud, Barranquilla 080002, Colombia

Zarate, R:
 Ctr Para Desarrollo Invest Cient, Asuncion 1255, Paraguay

Nakanishi, T:
 Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki 00014, Finland

 McGill Univ, Dept Human Genet, Montreal, PQ H3A 0G4, Canada

 McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada

 Kyoto Univ, Grad Sch Med, Kyoto McGill Int Collaborat Sch Genom Med, Kyoto 6068501, Japan

 Japan Soc Promot Sci, Tokyo 1020083, Japan

Pigazzini, S:
 Univ Milano Bicocca, I-20126 Milan, Italy

 Univ Helsinki, Inst Mol Med Finland, Helsinki 00014, Finland

Degenhardt, F:
 Univ Kiel, Inst Clin Mol Biol, D-24118 Kiel, Germany

 Univ Hosp Schleswig Holstein, Campus Kiel, D-24118 Kiel, Germany

Butler-Laporte, G:
 McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada

 McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 0G4, Canada

Maya-Miles, D:
 Univ Seville, Virgen Rocio Univ Hosp, Inst Biomed Seville, Digest Dis Unit, Seville 41103, Spain

 Inst Salud Carlos III, Ctr Biomed Network Res Hepat & Digest Dis CIBEREH, Madrid 28029, Spain

Bujanda, L:
 Inst Salud Carlos III, Ctr Biomed Network Res Hepat & Digest Dis CIBEREH, Madrid 28029, Spain

 Univ Basque Country, UPV EHU, Donostia Univ Hosp, Biodonostia Hlth Res Inst,Dept Liver & Gastrointe, San Sebastian 20014, Spain

Bouysran, Y:
 Univ Libre Bruxelles, Hop Erasme, Ctr Genet Humaine, B-1070 Brussels, Belgium

Palom, A:
 Hosp Univ Vall dHebron, Vall dHebron Barcelona Hosp Campus, Dept Internal Med, Liver Unit, Barcelona 08035, Spain

 Univ Autonoma Barcelona, Dept Med, Barcelona 08193, Spain

 Vall dHebron Inst Recerca VHIR, Liver Dis, Barcelona 08035, Spain

Ellinghaus, D:
 Univ Copenhagen, Novo Nordisk Fdn, Ctr Prot Res, Fac Hlth & Med Sci,Dis Syst Biol, DK-2200 Copenhagen, Denmark

Martinez-Bueno, M:
 Univ Granada, Pfizer, Andalusian Reg Govt, GENYO,Ctr Genom & Oncol Res, Granada 18016, Spain

Rolker, S:
 Univ Bonn, Univ Hosp Bonn, Med Fac, Inst Human Genet, D-53127 Bonn, Germany

Amitrano, S:
 Azienda Osped Univ Senese, Genet Med, I-53100 Siena, Italy

Roade, L:
 Inst Salud Carlos III, Ctr Biomed Network Res Hepat & Digest Dis CIBEREH, Madrid 28029, Spain

 Hosp Univ Vall dHebron, Vall dHebron Barcelona Hosp Campus, Dept Internal Med, Liver Unit, Barcelona 08035, Spain

 Univ Autonoma Barcelona, Dept Med, Barcelona 08193, Spain

Fava, F:
 Azienda Osped Univ Senese, Genet Med, I-53100 Siena, Italy

 Univ Siena, Med Genet, I-53100 Siena, Italy

 Univ Siena, Med Biotech Hub, I-53100 Siena, Italy

 Univ Siena, Competence Ctr, Dept Med Biotechnol, I-53100 Siena, Italy

Spinner, CD:
 Tech Univ Munich, Univ Hosp Rechts Isar, Sch Med, Dept Internal Med 2, D-80333 Munich, Germany

Prati, D:
 Univ Milan, Fdn IRCCS CaGranda Osped Maggiore Policlin, Dept Transfus Med & Hematol, I-20126 Milan, Italy

Bernardo, D:
 Inst Salud Carlos III, Ctr Biomed Network Res Hepat & Digest Dis CIBEREH, Madrid 28029, Spain

 Univ Valladolid, CSIC, Inst Biomed & Genet Mol IBGM, Unidad Excelencia,Mucosal Immunol Lab, Valladolid 47005, Spain

Garcia, F:
 Hosp Univ Clin San Cecilio, Granada 18016, Spain

 Inst Invest Ibs, Granada 18012, Spain

Darcis, G:
 Univ Liege, GIGA Inst, B-4000 Liege, Belgium

 Liege Univ Hosp, CHU Liege, B-4000 Liege, Belgium

Fernandez-Cadenas, I:
 Biomed Res Inst St Pau IIB St Pau, Stroke Pharmacogenom & Genet Grp, Barcelona 08041, Spain

Holter, JC:
 Oslo Univ Hosp, Dept Microbiol, N-0424 Oslo, Norway

 Univ Oslo, Inst Clin Med, N-0424 Oslo, Norway

Banales, JM:
 Inst Salud Carlos III, Ctr Biomed Network Res Hepat & Digest Dis CIBEREH, Madrid 28029, Spain

 Univ Basque Country, UPV EHU, Donostia Univ Hosp, Ikerbasque,Biodonostia Hlth Res Inst,Dept Liver &, San Sebastian 20014, Spain

Frithiof, R:
 Uppsala Univ, Dept Surg Sci Anaesthesiol & Intens Care Med, S-75105 Uppsala, Sweden

Duga, S:
 Humanitas Univ, Dept Biomed Sci, I-20089 Milan, Italy

 IRCCS Humanitas Res Hosp, I-20089 Milan, Italy

Asselta, R:
 Humanitas Univ, Dept Biomed Sci, I-20089 Milan, Italy

 IRCCS Humanitas Res Hosp, I-20089 Milan, Italy

Pereira, AC:
 Univ Sao Paulo, Med Sch, Heart Inst InCor, BR-05508070 Sao Paulo, Brazil

Romero-Gomez, M:
 Univ Seville, Virgen Rocio Univ Hosp, Inst Biomed Seville, Digest Dis Unit, Seville 41103, Spain

 Inst Salud Carlos III, Ctr Biomed Network Res Hepat & Digest Dis CIBEREH, Madrid 28029, Spain

Nafria-Jimenez, B:
 Osakidetza Basque Hlth Serv, Donostialdea Integrated Hlth Org, Clin Biochem Dept, San Sebastian 20006, Spain

Hov, JR:
 Univ Oslo, Inst Clin Med, N-0424 Oslo, Norway

 Oslo Univ Hosp, Norwegian PSC Res Ctr, N-0424 Oslo, Norway

 Oslo Univ Hosp, Dept Transplantat Med, Sect Gastroenterol, N-0424 Oslo, Norway

 Oslo Univ Hosp, Res Inst Internal Med, N-0424 Oslo, Norway

Migeotte, I:
 Univ Libre Bruxelles, Hop Erasme, Ctr Genet Humaine, B-1070 Brussels, Belgium

 Fonds Rech Sci FNRS, B-1000 Brussels, Belgium

Renieri, A:
 Azienda Osped Univ Senese, Genet Med, I-53100 Siena, Italy

 Univ Siena, Med Genet, I-53100 Siena, Italy

 Univ Siena, Med Biotech Hub, I-53100 Siena, Italy

 Univ Siena, Competence Ctr, Dept Med Biotechnol, I-53100 Siena, Italy

Planas, AM:
 Natl Spanish Res Council CSIC, Inst Biomed Res Barcelona IIBB, Barcelona 08028, Spain

 Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain

Ludwig, KU:
 Univ Bonn, Univ Hosp Bonn, Med Fac, Inst Human Genet, D-53127 Bonn, Germany

Buti, M:
 Inst Salud Carlos III, Ctr Biomed Network Res Hepat & Digest Dis CIBEREH, Madrid 28029, Spain

 Hosp Univ Vall dHebron, Vall dHebron Barcelona Hosp Campus, Dept Internal Med, Liver Unit, Barcelona 08035, Spain

 Univ Autonoma Barcelona, Dept Med, Barcelona 08193, Spain

Rahmouni, S:
 Univ Liege, GIGA Inst, B-4000 Liege, Belgium

Alarcon-Riquelme, ME:
 Univ Granada, Pfizer, Andalusian Reg Govt, GENYO,Ctr Genom & Oncol Res, Granada 18016, Spain

 Karolinska Inst, Inst Environm Med, S-17165 Solna, Sweden

Schulte, EC:
 Tech Univ Munich, Helmholtz Zentrum Munchen, Inst Virol, D-85764 Munich, Germany

 LMU Munich Univ, Univ Hosp, Inst Psychiat Phenom & Genom, D-80539 Munich, Germany

 LMU Munich Univ, Univ Hosp, Dept Psychiat, D-80539 Munich, Germany

Franke, A:
 Univ Kiel, Inst Clin Mol Biol, D-24118 Kiel, Germany

 Univ Hosp Schleswig Holstein, Campus Kiel, D-24118 Kiel, Germany

Karlsen, TH:
 Univ Oslo, Inst Clin Med, N-0424 Oslo, Norway

 Oslo Univ Hosp, Norwegian PSC Res Ctr, N-0424 Oslo, Norway

 Oslo Univ Hosp, Dept Transplantat Med, Sect Gastroenterol, N-0424 Oslo, Norway

 Oslo Univ Hosp, Res Inst Internal Med, N-0318 Oslo, Norway

Valenti, L:
 Univ Milan, Dept Pathopgysiol & Transplantat, I-20126 Milan, Italy

 Fdn IRCCS CaGranda Osped Maggiore Policlin, Dept Transfus Med & Hematol, Precis Med, I-20122 Milan, Italy

Zeberg, H:
 Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden

 Max Planck Inst Evolutionary Anthropol, D-04103 Leipzig, Germany

Richards, B:
 McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada

 McGill Univ, Dept Human Genet Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 0G4, Canada

 Kings Coll London, Dept Twin Res, London WC2R 2LS, England

Ganna, A:
 Univ Helsinki, Inst Mol Med Finland, Helsinki 00014, Finland

 Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02114 USA

Boada, M:
 Univ Int Catalunya, ACE Alzheimer Ctr Barcelona, Res Ctr, Barcelona 80828, Spain

 Univ Int Catalunya, ACE Alzheimer Ctr Barcelona, Memory Clin, Barcelona 08028, Spain

 Inst Salud Carlos III, Ctr Biomed Network Res Neurodegenerat Dis CIBERNE, Madrid 28029, Spain

de Rojas, I:
 Univ Int Catalunya, ACE Alzheimer Ctr Barcelona, Res Ctr, Barcelona 80828, Spain

 Univ Int Catalunya, ACE Alzheimer Ctr Barcelona, Memory Clin, Barcelona 08028, Spain

 Inst Salud Carlos III, Ctr Biomed Network Res Neurodegenerat Dis CIBERNE, Madrid 28029, Spain

Ruiz, A:
 Univ Int Catalunya, ACE Alzheimer Ctr Barcelona, Res Ctr, Barcelona 80828, Spain

 Univ Int Catalunya, ACE Alzheimer Ctr Barcelona, Memory Clin, Barcelona 08028, Spain

 Inst Salud Carlos III, Ctr Biomed Network Res Neurodegenerat Dis CIBERNE, Madrid 28029, Spain

Sanchez-Juan, P:
 CIEN Fdn, Queen Sofia Fdn, Alzheimer Ctr, Madrid 28031, Spain

Real, LM:
 Hosp Univ Valme, Unidad Clin Enfermedades Infecciosas & Microbiol, Seville 41014, Spain

Guillen-Navarro, E:
 Inst Murciano Invest Biosanitaria IMIB Arrixaca, Murcia, Spain

 Hosp Clin Univ Virgen Arrixaca, Serv Murciano Salud, Serv Pediat, Secc Genet Med, Murcia 30120, Spain

 Univ Murcia UMU, Fac Med, Dept Cirugia Pediat Obstet & Ginecol, Murcia 30100, Spain

 Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Grp Clin Vinculado, Madrid 28029, Spain

Ayuso, C:
 Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid 28029, Spain

 Univ Autonoma Madrid, Fdn Jimenez Diaz Univ Hosp, Inst Invest Sanitaria, UAM,FJD,IIS,Dept Genet & Genom, Madrid 28040, Spain

Gonzalez-Neira, A:
 Spanish Natl Canc Res Ctr, Human Genotyping CEGEN Unit, Madrid 28029, Spain

Riancho, JA:
 IDIVAL, Cantabria 39008, Spain

 Univ Cantabria, Cantabria 39008, Spain

 Hosp UM Valdecilla, Cantabria 39008, Spain

Rojas-Martinez, A:
 Tecnol Monterrey, Escuela Med & Ciencias Salud, Monterrey 64718, Mexico

Flores, C:
 Inst Tecnol & Energias Renovables, Genom Div, Santa Cruz De Tenerife 38600, Spain

 Univ Int Catalunya, ACE Alzheimer Ctr Barcelona, Res Ctr, Barcelona 80828, Spain

 Hosp Univ NS Candelaria, Res Unit, Santa Cruz De Tenerife 38010, Spain

 Inst Salud Carlos III, Ctr Biomed Network Res Resp Dis CIBERES, Madrid 28029, Spain

 Univ Fernando Pessoa, Fac Ciencias Salud, Las Palmas Gran Canaria 35450, Spain

Lapunzina, P:
 Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid 28029, Spain

 Hosp Univ La Paz IDIPAZ, Inst Genet Med & Mol INGEMM, Madrid 28046, Spain

 ERN, ITHACA, European Reference Network, Amsterdam, Netherlands

Carracedo, A:
 Univ Santiago de Compostela, Ctr Nacl Genotipado CEGEN, Santiago De Compostela 15706, Spain

 Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid 28029, Spain

 Inst Invest Sanitaria Santiago IDIS, Santiago De Compostela 15706, Spain

 Univ Santiago de Compostela, Ctr Singular Invest Med Mol & Enfermedades Cronic, Santiago De Compostela 15782, Spain

 Fdn Publ Galegade Med Xenom, Sistema Galegode Saude SERGAS, Santiago De Compostela 15706, Spain
ISSN: 09646906
Editorial
OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND, Reino Unido
Tipo de documento: Article
Volumen: 31 Número: 22
Páginas: 3789-3806
WOS Id: 000840360300001
ID de PubMed: 35708486
imagen hybrid, Green Published, Hybrid Gold, Green

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