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Sci Rep
. 2024 Feb 6;14(1):3000.
doi: 10.1038/s41598-024-53310-x. A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death
Francesca Minnai # 1 2 , Filippo Biscarini # 3 , Martina Esposito 1 , Tommaso A Dragani 4 , Luis Bujanda 5 , Souad Rahmouni 6 , Marta E Alarcón-Riquelme 7 8 , David Bernardo 9 10 , Elena Carnero-Montoro 7 11 , Maria Buti 12 , Hugo Zeberg 13 , Rosanna Asselta 14 15 , Manuel Romero-Gómez 16 ; GEN-COVID Multicenter Study; Israel Fernandez-Cadenas 17 , Chiara Fallerini 18 19 , Kristina Zguro 18 19 , Susanna Croci 18 19 , Margherita Baldassarri 18 19 , Mirella Bruttini 18 19 20 , Simone Furini 21 , Alessandra Renieri 18 19 20 , Francesca Colombo 22
Collaborators, Affiliations
The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10-8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10-8). A total of 113 variants were associated with survival at P-value < 1.0 × 10-5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways.
. 2024 Feb 6;14(1):3000.
doi: 10.1038/s41598-024-53310-x. A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death
Francesca Minnai # 1 2 , Filippo Biscarini # 3 , Martina Esposito 1 , Tommaso A Dragani 4 , Luis Bujanda 5 , Souad Rahmouni 6 , Marta E Alarcón-Riquelme 7 8 , David Bernardo 9 10 , Elena Carnero-Montoro 7 11 , Maria Buti 12 , Hugo Zeberg 13 , Rosanna Asselta 14 15 , Manuel Romero-Gómez 16 ; GEN-COVID Multicenter Study; Israel Fernandez-Cadenas 17 , Chiara Fallerini 18 19 , Kristina Zguro 18 19 , Susanna Croci 18 19 , Margherita Baldassarri 18 19 , Mirella Bruttini 18 19 20 , Simone Furini 21 , Alessandra Renieri 18 19 20 , Francesca Colombo 22
Collaborators, Affiliations
- PMID: 38321133
- DOI: 10.1038/s41598-024-53310-x
The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10-8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10-8). A total of 113 variants were associated with survival at P-value < 1.0 × 10-5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways.