ccf31c6805ca1474b7494bd7af8a55b3 pmc_34945790.pdf 20040bb2a911f639622fea14179f7724874d5ca4 pmc_34945790.pdf c31825337cabb2058a7cdf7524d3cb0ecf79cfc2e52882736186dca9cabce5e6 pmc_34945790.pdf Title: Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study Subject: 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. Keywords: SARS-CoV-2; COVID-19; GWAS; GR@ACE/DEGESCO; dementia; APOE Author: Itziar de Rojas, Isabel Hernández, Laura Montrreal, Inés Quintela, Miguel Calero, Jose Luís Royo, Raquel Huerto Vilas, Antonio González-Pérez, Emilio Franco-Macías, Juan Macías, Manuel Menéndez-González, Ana Frank-García, Mónica Diez-Fairen, Carmen Lage, Sebastián García-Madrona, Nuria Aguilera, Pablo García-González, Raquel Puerta, Oscar Sotolongo-Grau, Silvia Alonso-Lana, Alberto Rábano, Alfonso Arias Pastor, Ana Belén Pastor, Anaïs Corma-Gómez, Angel Martín Montes, Carmen Martínez Rodríguez, Dolores Buiza-Rueda, Maria Teresa Periñán, Eloy Rodriguez-Rodriguez, Ignacio Alvarez, Irene Rosas Allende, Juan A. Pineda, María Bernal Sánchez-Arjona, Marta Fernández-Fuertes, Silvia Mendoza, Teodoro del Ser, GR@ACE/DEGESCO Consortium, Guillermo Garcia-Ribas, Pascual Sánchez-Juan, Pau Pastor, María J. Bullido, Victoria Álvarez, Luis M. Real, Pablo Mir, Gerard Piñol-Ripoll, Jose María García-Alberca, Miguel Medina, Adelina Orellana, Chris R. 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Pineda, María Bernal Sánchez-Arjona, Marta Fernández-Fuertes, Silvia Mendoza, Teodoro del Ser, GR@ACE/DEGESCO Consortium, Guillermo Garcia-Ribas, Pascual Sánchez-Juan, Pau Pastor, María J. Bullido, Victoria Álvarez, Luis M. Real, Pablo Mir, Gerard Piñol-Ripoll, Jose María García-Alberca, Miguel Medina, Adelina Orellana, Chris R. Butler, Marta Marquié, María Eugenia Sáez, Ángel Carracedo, Lluís Tárraga, Mercè Boada and Agustín Ruiz Subject: 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. 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