Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study

Journal of Personalized Medicine

GR@ACE/DEGESCO Consortium¹  Silvia Mendoza²  María Eugenia Sáez³  Antonio González-Pérez³  Maria Teresa Periñán⁴  María J. Bullido⁴  Pablo Mir⁴  Eloy Rodriguez-Rodriguez⁴  Miguel Medina⁴  Miguel Calero⁴  Jose María García-Alberca⁴  Dolores Buiza-Rueda⁴  Ana Frank-García⁴  Carmen Lage⁴  Angel Martín Montes⁴  Pascual Sánchez-Juan⁴  Alberto Rábano⁴  Ana Belén Pastor⁵  Teodoro del Ser⁶  Jose Luís Royo⁷  Mónica Diez-Fairen⁸  Ignacio Alvarez⁸  Pau Pastor⁸  Ángel Carracedo⁹  Inés Quintela⁹  Sebastián García-Madrona^1,10  Guillermo Garcia-Ribas^1,10  Irene Rosas Allende^1,11  Carmen Martínez Rodríguez^1,11  Victoria Álvarez^1,11  Marta Marquié^1,12  Mercè Boada^1,12  Itziar de Rojas^1,12  Silvia Alonso-Lana^1,12  Isabel Hernández^1,12  Oscar Sotolongo-Grau^1,12  Lluís Tárraga^1,12  Nuria Aguilera^1,12  Agustín Ruiz^1,12  Chris R. Butler^1,12  Raquel Puerta^1,12  Pablo García-González^1,12  Adelina Orellana^1,12  Laura Montrreal^1,12  Manuel Menéndez-González^1,13  Marta Fernández-Fuertes^1,14  Juan A. Pineda^1,14  Anaïs Corma-Gómez^1,14  Juan Macías^1,14  Luis M. Real^1,14  Emilio Franco-Macías^1,15  María Bernal Sánchez-Arjona^1,15  Alfonso Arias Pastor^1,16  Raquel Huerto Vilas^1,16  Gerard Piñol-Ripoll^1,16 

[1] ;Alzheimer Research Center & Memory Clinic, Andalusian Institute for Neuroscience, 29012 Málaga, Spain;CAEBI, Centro Andaluz de Estudios Bioinformáticos, 41013 Sevilla, Spain;CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, 28220 Madrid, Spain;CIEN Foundation/Queen Sofia Foundation Alzheimer Center, 28220 Madrid, Spain;Department of Neurology/CIEN Foundation/Queen Sofia Foundation Alzheimer Center, 28220 Madrid, Spain;Depatamento de Especialidades Quirúrgicas, Bioquímica e Inmunología, Facultad de Medicina, Universidad de Málaga, 29016 Málaga, Spain;Fundació Docència i Recerca MútuaTerrassa, 08221 Terrassa, Spain;Grupo de Medicina Xenómica, Centro Nacional de Genotipado (CEGEN-PRB3-ISCIII), Universidade de Santiago de Compostela, 15705 Santiago de Compostela, Spain;Hospital Universitario Ramon y Cajal, IRYCIS, 28034 Madrid, Spain;Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Asturias, Spain;Research Center and Memory Clinic, Ace Alzheimer Center Barcelona—Universitat Internacional de Catalunya, 08017 Barcelona, Spain;Servicio de Neurología, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain;Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, 41013 Sevilla, Spain;Unidad de Demencias, Servicio de Neurología y Neurofisiología, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain;Unitat Trastorns Cognitius, Hospital Universitari Santa Maria de Lleida, 25198 Lleida, Spain;

关键词: SARS-CoV-2;    COVID-19;    GWAS;    GR@ACE/DEGESCO;    dementia;    APOE;   

DOI  :  10.3390/jpm11121318

来源: DOAJ

【 摘 要 】

Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis.

【 授权许可】

Unknown