Characterization of caffeine response regulatory variants in vascular endothelial cells
- Wayne State University, United States
- University of Michigan-Ann Arbor, United States
Abstract
Genetic variants in gene regulatory sequences can modify gene expression and mediate the molecular response to environmental stimuli. In addition, genotype-environment interactions (GxE) contribute to complex traits such as cardiovascular disease. Caffeine is the most widely consumed stimulant and is known to produce a vascular response. To investigate GxE for caffeine, we treated vascular endothelial cells with caffeine and used a massively parallel reporter assay to measure allelic effects on gene regulation for over 43,000 genetic variants. We identified 665 variants with allelic effects on gene regulation and 29 variants that regulate the gene expression response to caffeine (GxE, FDR<10%). When overlapping our GxE results with eQTLs colocalized with CAD and hypertension, we dissected their regulatory mechanisms and showed a modulatory role for caffeine. Our results demonstrate that massively parallel reporter assay is a powerful approach to identify and molecularly characterize GxE in the specific context of caffeine consumption.
Data availability
FASTQ files and read count data are available at the GEO accession number GSE221514
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Characterization of caffeine response regulatory variants in vascular endothelial cellsNCBI Gene Expression Omnibus, GSE221514.
Article and author information
Author details
Funding
National Institute of General Medical Sciences (R01GM109215)
- Roger Pique-Regi
- Francesca Luca
National Institute of Environmental Health Sciences (R01ES033634)
- Xiaoquan Wen
- Roger Pique-Regi
- Francesca Luca
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Stephen CJ Parker, University of Michigan, United States
Version history
- Preprint posted: November 24, 2022 (view preprint)
- Received: November 30, 2022
- Accepted: February 8, 2024
- Accepted Manuscript published: February 9, 2024 (version 1)
- Version of Record published: February 28, 2024 (version 2)
Copyright
© 2024, Boye et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Characterization of caffeine response regulatory variants in vascular endothelial cells
eLife 13:e85235.
https://doi.org/10.7554/eLife.85235
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