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Epigenetic variation impacts individual differences in the transcriptional response to influenza infection.
Aracena, Katherine A; Lin, Yen-Lung; Luo, Kaixuan; Pacis, Alain; Gona, Saideep; Mu, Zepeng; Yotova, Vania; Sindeaux, Renata; Pramatarova, Albena; Simon, Marie-Michelle; Chen, Xun; Groza, Cristian; Lougheed, David; Gregoire, Romain; Brownlee, David; Boye, Carly; Pique-Regi, Roger; Li, Yang; He, Xin; Bujold, David; Pastinen, Tomi; Bourque, Guillaume; Barreiro, Luis B.
Afiliação
  • Aracena KA; Department of Human Genetics, University of Chicago, Chicago, IL, USA.
  • Lin YL; Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA.
  • Luo K; Department of Human Genetics, University of Chicago, Chicago, IL, USA.
  • Pacis A; Canadian Centre for Computational Genomics, McGill University, Montreal, Quebec, Canada.
  • Gona S; Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA.
  • Mu Z; Department of Human Genetics, University of Chicago, Chicago, IL, USA.
  • Yotova V; Department of Genetics, CHU Sainte-Justine Research Center, Montreal, Quebec, Canada.
  • Sindeaux R; Department of Genetics, CHU Sainte-Justine Research Center, Montreal, Quebec, Canada.
  • Pramatarova A; McGill Genome Centre, Montreal, Quebec, Canada.
  • Simon MM; McGill Genome Centre, Montreal, Quebec, Canada.
  • Chen X; Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan.
  • Groza C; Quantitative Life Sciences, McGill University, Montreal, Quebec, Canada.
  • Lougheed D; Canadian Centre for Computational Genomics, McGill University, Montreal, Quebec, Canada.
  • Gregoire R; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
  • Brownlee D; Canadian Centre for Computational Genomics, McGill University, Montreal, Quebec, Canada.
  • Boye C; Canadian Centre for Computational Genomics, McGill University, Montreal, Quebec, Canada.
  • Pique-Regi R; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA.
  • Li Y; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA.
  • He X; Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA.
  • Bujold D; Department of Human Genetics, University of Chicago, Chicago, IL, USA.
  • Pastinen T; Department of Human Genetics, University of Chicago, Chicago, IL, USA.
  • Bourque G; Canadian Centre for Computational Genomics, McGill University, Montreal, Quebec, Canada.
  • Barreiro LB; McGill Genome Centre, Montreal, Quebec, Canada.
Nat Genet ; 56(3): 408-419, 2024 Mar.
Article em En | MEDLINE | ID: mdl-38424460
ABSTRACT
Humans display remarkable interindividual variation in their immune response to identical challenges. Yet, our understanding of the genetic and epigenetic factors contributing to such variation remains limited. Here we performed in-depth genetic, epigenetic and transcriptional profiling on primary macrophages derived from individuals of European and African ancestry before and after infection with influenza A virus. We show that baseline epigenetic profiles are strongly predictive of the transcriptional response to influenza A virus across individuals. Quantitative trait locus (QTL) mapping revealed highly coordinated genetic effects on gene regulation, with many cis-acting genetic variants impacting concomitantly gene expression and multiple epigenetic marks. These data reveal that ancestry-associated differences in the epigenetic landscape can be genetically controlled, even more than gene expression. Lastly, among QTL variants that colocalized with immune-disease loci, only 7% were gene expression QTL, while the remaining genetic variants impact epigenetic marks, stressing the importance of considering molecular phenotypes beyond gene expression in disease-focused studies.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Influenza Humana Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Influenza Humana Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos