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

Interpreting coronary artery disease risk through gene-environment interactions in gene regulation

Anthony S Findley, Allison L Richards, Cristiano Petrini, Adnan Alazizi, Elizabeth Doman, Alexander G Shanku, Omar Davis, Nancy Hauff, Yoram Sorokin, Xiaoquan Wen, Roger Pique-Regi, View ORCID ProfileFrancesca Luca
doi: https://doi.org/10.1101/475483
Anthony S Findley
1Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan 48201, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Allison L Richards
1Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan 48201, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cristiano Petrini
1Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan 48201, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Adnan Alazizi
1Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan 48201, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elizabeth Doman
1Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan 48201, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexander G Shanku
1Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan 48201, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Omar Davis
1Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan 48201, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nancy Hauff
2Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan 48201, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yoram Sorokin
2Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan 48201, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaoquan Wen
3Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roger Pique-Regi
1Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan 48201, USA
2Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan 48201, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: fluca@wayne.edu rpique@wayne.edu
Francesca Luca
1Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan 48201, USA
2Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan 48201, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Francesca Luca
  • For correspondence: fluca@wayne.edu rpique@wayne.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

GWAS and eQTL studies identified thousands of genetic variants associated with complex traits and gene expression. Despite the important role of environmental exposures in complex traits, only a limited number of environmental factors are measured in these studies. Measuring molecular phenotypes in tightly controlled cellular environments provides a more tractable setting to study gene-environment interactions in the absence of other confounding variables.

We performed RNA-seq and ATAC-seq in endothelial cells exposed to retinoic acid, dexamethasone, caffeine, and selenium to model genetic and environmental effects on gene regulation in the vascular endothelium, a common site of pathology in cardiovascular disease. We found that genes near regions of differentially accessible chromatin were more likely to be differentially expressed (OR = [3.41, 6.52], p < 10−16). Furthermore, we confirmed that environment-specific changes in transcription factor binding are a key mechanism for cellular response to environmental stimuli. SNPs in these transcription response factor footprints for dexamethasone, caffeine, and retinoic acid were enriched in GTEx eQTLs from artery tissues indicating that these environmental conditions are latently present in GTEx samples. Additionally, SNPs in footprints for response factors in caffeine are enriched in colocalized eQTLs for coronary artery disease (CAD), suggesting a role for caffeine in CAD risk. Interestingly, each treatment may amplify or buffer genetic risk for CAD, depending on the particular SNP considered.

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-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted November 23, 2018.
Download PDF
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.
Interpreting coronary artery disease risk through gene-environment interactions in gene regulation
(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
Interpreting coronary artery disease risk through gene-environment interactions in gene regulation
Anthony S Findley, Allison L Richards, Cristiano Petrini, Adnan Alazizi, Elizabeth Doman, Alexander G Shanku, Omar Davis, Nancy Hauff, Yoram Sorokin, Xiaoquan Wen, Roger Pique-Regi, Francesca Luca
bioRxiv 475483; doi: https://doi.org/10.1101/475483
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Interpreting coronary artery disease risk through gene-environment interactions in gene regulation
Anthony S Findley, Allison L Richards, Cristiano Petrini, Adnan Alazizi, Elizabeth Doman, Alexander G Shanku, Omar Davis, Nancy Hauff, Yoram Sorokin, Xiaoquan Wen, Roger Pique-Regi, Francesca Luca
bioRxiv 475483; doi: https://doi.org/10.1101/475483

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

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (2505)
  • Biochemistry (4951)
  • Bioengineering (3452)
  • Bioinformatics (15127)
  • Biophysics (6854)
  • Cancer Biology (5357)
  • Cell Biology (7681)
  • Clinical Trials (138)
  • Developmental Biology (4502)
  • Ecology (7110)
  • Epidemiology (2059)
  • Evolutionary Biology (10178)
  • Genetics (7491)
  • Genomics (9750)
  • Immunology (4801)
  • Microbiology (13131)
  • Molecular Biology (5109)
  • Neuroscience (29289)
  • Paleontology (203)
  • Pathology (832)
  • Pharmacology and Toxicology (1454)
  • Physiology (2116)
  • Plant Biology (4714)
  • Scientific Communication and Education (1002)
  • Synthetic Biology (1332)
  • Systems Biology (3993)
  • Zoology (766)