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.

A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death / Minnai F.; Biscarini F.; Esposito M.; Dragani T.A.; Bujanda L.; Rahmouni S.; Alarcon-Riquelme M.E.; Bernardo D.; Carnero-Montoro E.; Buti M.; Zeberg H.; Asselta R.; Romero-Gomez M.; Fernandez-Cadenas I.; Fallerini C.; Zguro K.; Croci S.; Baldassarri M.; Bruttini M.; Furini S.; Renieri A.; Colombo F.; Mari F.; Daga S.; Meloni I.; Brunelli G.; Lista M.; Maffeo D.; Pasquinelli E.; Antolini E.; Basso S.L.; Minetto S.; Rollo G.; Rina A.; Rozza M.; Tita R.; Mencarelli M.A.; Rizzo C.L.; Pinto A.M.; Ariani F.; Montagnani F.; Tumbarello M.; Rancan I.; Fabbiani M.; Cameli P.; Bennett D.; Anedda F.; Marcantonio S.; Scolletta S.; Franchi F.; Mazzei M.A.; Guerrini S.; Conticini E.; Cantarini L.; Frediani B.; Tacconi D.; Raffaelli C.S.; Emiliozzi A.; Feri M.; Donati A.; Scala R.; Guidelli L.; Spargi G.; Corridi M.; Nencioni C.; Croci L.; Caldarelli G.P.; Romani D.; Piacentini P.; Bandini M.; Desanctis E.; Cappelli S.; Canaccini A.; Verzuri A.; Anemoli V.; Ognibene A.; Lorubbio M.; Pancrazzi A.; Vaghi M.; Monforte A.D.; Miraglia F.G.; Mondelli M.U.; Mantovani S.; Bruno R.; Vecchia M.; Maffezzoni M.; Martinelli E.; Girardis M.; Busani S.; Venturelli S.; Cossarizza A.; Antinori A.; Vergori A.; Rusconi S.; Siano M.; Gabrieli A.; Riva A.; Francisci D.; Schiaroli E.; Pallotto C.; Parisi S.G.; Basso M.; Panese S.; Baratti S.; Scotton P.G.; Andretta F.; Giobbia M.; Scaggiante R.; Gatti F.; Castelli F.; Quiros-Roldan E.; Antoni M.D.; Zanella I.; Monica M.D.; Piscopo C.; Capasso M.; Russo R.; Andolfo I.; Iolascon A.; Fiorentino G.; Carella M.; Castori M.; Merla G.; Squeo G.M.; Aucella F.; Raggi P.; Perna R.; Bassetti M.; Di Biagio A.; Sanguinetti M.; Masucci L.; Guarnaccia A.; Valente S.; Di Florio A.; Mandala M.; Giorli A.; Salerni L.; Zucchi P.; Parravicini P.; Menatti E.; Trotta T.; Giannattasio F.; Coiro G.; Lacerenza G.; Mussini C.; Tavecchia L.; Crotti L.; Parati G.; Mene R.; Sanarico M.; Gori M.; Raimondi F.; Stella A.; Biscarini F.; Bachetti T.; La Rovere M.T.; Bussotti M.; Ludovisi S.; Capitani K.; Dei S.; Ravaglia S.; Giliberti A.; Gori G.; Artuso R.; Andreucci E.; Perrella A.; Bianchi F.; Bergomi P.; Catena E.; Colombo R.; Luchi S.; Morelli G.; Petrocelli P.; Iacopini S.; Modica S.; Baroni S.; Micheli G.; Falcone M.; Urso D.; Tiseo G.; Matucci T.; Pulcinelli A.; Grassi D.; Ferri C.; Marinangeli F.; Brancati F.; Vincenti A.; Borgo V.; Lombardi S.; Lenzi M.; Di Pietro M.A.; Attala L.; Costa C.; Gabbuti A.; Bellucci A.; Colaneri M.; Casprini P.; Pomara C.; Esposito M.; Leoncini R.; Cirianni M.; Galasso L.; Bellini M.A.; Gabbi C.; Picchiotti N.; Furini S.; Pelo E.; Minuti B.; Gerundino F.; Lazzeri C.; Vecchi A.; Bianchi L.; Venturini E.; Montagnani C.; Chiappini E.; Beltrami C.; Galli L.. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - ELETTRONICO. - 14:(2024), pp. 3000.0-3000.0. [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

Biscarini F.;Bernardo D.;Croci S.;Baldassarri M.;Renieri A.;Pasquinelli E.;Rizzo C. L.;Ariani F.;Montagnani F.;Tumbarello M.;Rancan I.;Cameli P.;Franchi F.;Mazzei M. A.;Tacconi D.;Feri M.;Donati A.;Scala R.;Cappelli S.;Ognibene A.;Lorubbio M.;Pancrazzi A.;Venturelli S.;Vergori A.;Siano M.;Riva A.;Baratti S.;Andretta F.;Gatti F.;Castelli F.;Piscopo C.;Capasso M.;Russo R.;Iolascon A.;Fiorentino G.;Merla G.;Raggi P.;Di Biagio A.;Di Florio A.;Salerni L.;Zucchi P.;Giannattasio F.;Gori M.;Raimondi F.;Biscarini F.;Bussotti M.;Capitani K.;Gori G.;Artuso R.;Andreucci E.;Bianchi F.;Bergomi P.;Iacopini S.;Modica S.;Micheli G.;Matucci T.;Borgo V.;Attala L.;Gabbuti A.;Bellucci A.;Pomara C.;Leoncini R.;Pelo E.;Gerundino F.;Bianchi L.;Venturini E.;Montagnani C.;Chiappini E.;Beltrami C.;Galli L.
2024

Abstract

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
14
0
0
Minnai F.; Biscarini F.; Esposito M.; Dragani T.A.; Bujanda L.; Rahmouni S.; Alarcon-Riquelme M.E.; Bernardo D.; Carnero-Montoro E.; Buti M.; Zeberg H...espandi
File in questo prodotto:
File Dimensione Formato  
s41598-024-53310-x.pdf

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: Open Access
Dimensione 1.94 MB
Formato Adobe PDF
1.94 MB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1402434
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 0
social impact