Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Epigenetic variation impacts ancestry-associated differences in the transcriptional response to influenza infection

View ORCID ProfileKatherine A Aracena, View ORCID ProfileYen-Lung Lin, View ORCID ProfileKaixuan Luo, View ORCID ProfileAlain Pacis, Saideep Gona, View ORCID ProfileZepeng Mu, View ORCID ProfileVania Yotova, View ORCID ProfileRenata Sindeaux, View ORCID ProfileAlbena Pramatarova, Marie-Michelle Simon, View ORCID ProfileXun Chen, View ORCID ProfileCristian Groza, View ORCID ProfileDavid Lougheed, Romain Gregoire, David Brownlee, View ORCID ProfileYang Li, Xin He, David Bujold, View ORCID ProfileTomi Pastinen, View ORCID ProfileGuillaume Bourque, View ORCID ProfileLuis B Barreiro
doi: https://doi.org/10.1101/2022.05.10.491413
Katherine A Aracena
1Department of Human Genetics, University of Chicago, Chicago, IL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Katherine A Aracena
Yen-Lung Lin
2Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Yen-Lung Lin
Kaixuan Luo
1Department of Human Genetics, University of Chicago, Chicago, IL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kaixuan Luo
Alain Pacis
3Canadian Centre for Computational Genomics, McGill University, Montreal, QC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alain Pacis
Saideep Gona
2Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zepeng Mu
1Department of Human Genetics, University of Chicago, Chicago, IL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Zepeng Mu
Vania Yotova
4Department of Genetics, CHU Sainte-Justine Research Center, Montreal, QC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Vania Yotova
Renata Sindeaux
4Department of Genetics, CHU Sainte-Justine Research Center, Montreal, QC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Renata Sindeaux
Albena Pramatarova
5McGill Genome Centre, Montreal, QC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Albena Pramatarova
Marie-Michelle Simon
5McGill Genome Centre, Montreal, QC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xun Chen
9Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Xun Chen
Cristian Groza
10Quantitative Life Science, McGill University, Montreal, QC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Cristian Groza
David Lougheed
3Canadian Centre for Computational Genomics, McGill University, Montreal, QC, Canada
6Department of Human Genetics, McGill University, Montreal, QC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for David Lougheed
Romain Gregoire
3Canadian Centre for Computational Genomics, McGill University, Montreal, QC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Brownlee
3Canadian Centre for Computational Genomics, McGill University, Montreal, QC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yang Li
1Department of Human Genetics, University of Chicago, Chicago, IL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Yang Li
Xin He
1Department of Human Genetics, University of Chicago, Chicago, IL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Bujold
3Canadian Centre for Computational Genomics, McGill University, Montreal, QC, Canada
5McGill Genome Centre, Montreal, QC, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tomi Pastinen
6Department of Human Genetics, McGill University, Montreal, QC, Canada
7Genomic Medicine Center, Children’s Mercy, Kansas City, MO, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Tomi Pastinen
Guillaume Bourque
3Canadian Centre for Computational Genomics, McGill University, Montreal, QC, Canada
5McGill Genome Centre, Montreal, QC, Canada
6Department of Human Genetics, McGill University, Montreal, QC, Canada
9Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Guillaume Bourque
  • For correspondence: lbarreiro@uchicago.edu guil.bourque@mcgill.ca
Luis B Barreiro
1Department of Human Genetics, University of Chicago, Chicago, IL, USA
2Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA
8Committee on Immunology, University of Chicago, Chicago, IL, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Luis B Barreiro
  • For correspondence: lbarreiro@uchicago.edu guil.bourque@mcgill.ca
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Summary

Humans display remarkable inter-individual variation in immune response when exposed to identical immune challenges. Yet, our understanding of the genetic and epigenetic factors contributing to such variation remains limited. Here we carried out in-depth genetic, epigenetic, and transcriptional profiling on primary macrophages derived from a panel of European and African-ancestry individuals before and after infection with influenza A virus (IAV). We show that baseline epigenetic profiles are strongly predictive of the transcriptional response to IAV across individuals, and that ancestry-associated differences in gene expression are tightly coupled with variation in enhancer activity. 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 are genetically controlled, even more so than variation in gene expression. Lastly, we show that among QTL variants that colocalized with immune-disease loci, only 7% were gene expression QTL, the remaining corresponding to genetic variants that impact one or more epigenetic marks, which stresses the importance of considering molecular phenotypes beyond gene expression in disease-focused studies.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted May 11, 2022.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Epigenetic variation impacts ancestry-associated differences in the transcriptional response to influenza infection
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Epigenetic variation impacts ancestry-associated differences in the transcriptional response to influenza infection
Katherine A Aracena, Yen-Lung Lin, Kaixuan Luo, Alain Pacis, Saideep Gona, Zepeng Mu, Vania Yotova, Renata Sindeaux, Albena Pramatarova, Marie-Michelle Simon, Xun Chen, Cristian Groza, David Lougheed, Romain Gregoire, David Brownlee, Yang Li, Xin He, David Bujold, Tomi Pastinen, Guillaume Bourque, Luis B Barreiro
bioRxiv 2022.05.10.491413; doi: https://doi.org/10.1101/2022.05.10.491413
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Epigenetic variation impacts ancestry-associated differences in the transcriptional response to influenza infection
Katherine A Aracena, Yen-Lung Lin, Kaixuan Luo, Alain Pacis, Saideep Gona, Zepeng Mu, Vania Yotova, Renata Sindeaux, Albena Pramatarova, Marie-Michelle Simon, Xun Chen, Cristian Groza, David Lougheed, Romain Gregoire, David Brownlee, Yang Li, Xin He, David Bujold, Tomi Pastinen, Guillaume Bourque, Luis B Barreiro
bioRxiv 2022.05.10.491413; doi: https://doi.org/10.1101/2022.05.10.491413

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genetics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4087)
  • Biochemistry (8762)
  • Bioengineering (6479)
  • Bioinformatics (23341)
  • Biophysics (11750)
  • Cancer Biology (9149)
  • Cell Biology (13247)
  • Clinical Trials (138)
  • Developmental Biology (7416)
  • Ecology (11369)
  • Epidemiology (2066)
  • Evolutionary Biology (15087)
  • Genetics (10399)
  • Genomics (14009)
  • Immunology (9121)
  • Microbiology (22040)
  • Molecular Biology (8779)
  • Neuroscience (47367)
  • Paleontology (350)
  • Pathology (1420)
  • Pharmacology and Toxicology (2482)
  • Physiology (3704)
  • Plant Biology (8050)
  • Scientific Communication and Education (1431)
  • Synthetic Biology (2208)
  • Systems Biology (6016)
  • Zoology (1249)