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Genome-wide epistasis study highlights genetic interactions influencing severity of COVID-19.
Lin, Shiqi; Gao, Xingjian; Degenhardt, Frauke; Qian, Yu; Liu, Tianzi; Ramon, Xavier Farre; Hadi, Syed Sibte; Romero-Gómez, Manuel; Fernández, Javier; Albillos, Agustín; Ferret, Maria Buti; Bujanda, Luis; Julià, Antonio; de Cid, Rafael; Asselta, Rosanna; Franke, Andre; Liu, Fan.
Afiliación
  • Lin S; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China.
  • Gao X; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Degenhardt F; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China.
  • Qian Y; National Clinical Research Center for Kidney Diseases, Jinling Hospital, 305 East Zhongshan Road, Nanjing, China.
  • Liu T; Institute of Clinical Molecular Biology and University Hospital of Schleswig-Holstein, Christian-Albrechts-University, Rosalind-Franklin-Str. 12, 24105, Kiel, Germany.
  • Ramon XF; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China.
  • Hadi SS; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Romero-Gómez M; CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China.
  • Fernández J; Genomes for Life-GCAT Lab., Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain.
  • Albillos A; Department of Forensic Sciences, College of Criminal Justice, Naif Arab University of Security Sciences, 11452, Riyadh, Kingdom of Saudi Arabia.
  • Ferret MB; Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
  • Bujanda L; Instituto de Biomedicina de Sevilla (IBIS), Seville, Spain.
  • Julià A; University of Sevilla, Seville, Spain.
  • de Cid R; Digestive Diseases Unit, Institute of Biomedicine of Seville, Virgen del Rocio University Hospital, University of Seville, Seville, Spain.
  • Asselta R; Hospital Clinic, University of Barcelona, and IDIBAPS, Barcelona, Spain.
  • Franke A; European Foundation for the Study of Chronic Liver Failure (EF-CLIF), Barcelona, Spain.
  • Liu F; Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
Eur J Epidemiol ; 38(8): 883-889, 2023 Aug.
Article en En | MEDLINE | ID: mdl-37358671
Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to life-threatening respiratory symptoms. Understanding the genetic basis of the prognosis of COVID-19 is important for risk profiling of potentially severe symptoms. Here, we conducted a genome-wide epistasis study of COVID-19 severity in 2243 patients with severe symptoms and 12,612 patients with no or mild symptoms from the UK Biobank, followed by a replication study in an independent Spanish cohort (1416 cases, 4382 controls). Our study highlighted 3 interactions with genome-wide significance in the discovery phase, nominally significant in the replication phase, and enhanced significance in the meta-analysis. For example, the lead interaction was found between rs9792388 upstream of PDGFRL and rs3025892 downstream of SNAP25, where the composite genotype of rs3025892 CT and rs9792388 CA/AA showed higher risk of severe disease than any other genotypes (P = 2.77 × 10-12, proportion of severe cases = 0.24 ~ 0.29 vs. 0.09 ~ 0.18, genotypic OR = 1.96 ~ 2.70). This interaction was replicated in the Spanish cohort (P = 0.002, proportion of severe cases = 0.30 ~ 0.36 vs. 0.14 ~ 0.25, genotypic OR = 1.45 ~ 2.37) and showed enhanced significance in the meta-analysis (P = 4.97 × 10-14). Notably, these interactions indicated a possible molecular mechanism by which SARS-CoV-2 affects the nervous system. The first exhaustive genome-wide screening for epistasis improved our understanding of genetic basis underlying the severity of COVID-19.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: COVID-19 Tipo de estudio: Systematic_reviews Límite: Humans Idioma: En Revista: Eur J Epidemiol Asunto de la revista: EPIDEMIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: COVID-19 Tipo de estudio: Systematic_reviews Límite: Humans Idioma: En Revista: Eur J Epidemiol Asunto de la revista: EPIDEMIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos