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Series GSE126199 Query DataSets for GSE126199
Status Public on Jun 25, 2019
Title Integrative vascular endothelial cell genomics identify AIDA as a coronary artery disease candidate gene (Hi-C)
Organism Homo sapiens
Experiment type Other
Summary Genome-wide association studies (GWAS) have identified 100s of loci associated with coronary artery disease (CAD) and blood pressure (BP)/hypertension. Many of these loci are not associated with traditional risk factors, nor include obvious candidate genes, complicating their functional characterization. We hypothesized that many GWAS loci associated with vascular diseases modulate endothelial functions. Endothelial cells play critical roles in regulating vascular homeostasis (e.g. selective barrier, inflammation, hemostasis, vascular tone) and endothelial dysfunction is a hallmark of atherosclerosis and hypertension. We generated an integrated map of gene expression (RNA-sequencing), open chromatin regions (ATAC-sequencing), and 3D interactions (Hi-C) in resting and TNFα-treated human endothelial cells. We showed that genetic variants associated with CAD and BP are enriched in open chromatin regions identified in endothelial cells. We used physical loops identified by Hi-C to link open chromatin peaks that include CAD or BP SNPs with the promoter of genes expressed in endothelial cells. This analysis highlighted 4,548 combinations of regulatory elements-promoters, including 108 pairs that involve a differentially open chromatin site and a differentially expressed gene following TNFα treatment. At a CAD locus, we validated one of these pairs by engineering a deletion of the TNFα-sensitive regulatory element using CRISPR/Cas9 and measuring an effect on the expression of the novel CAD candidate gene AIDA. Our data support an important role played by genetic variants acting in the vascular endothelium to modulate inter-individual risk in CAD or hypertension
Overall design Hi-C of TNF-alpha treated endothelial cells (teloHAEC) for 0h or 4h
Contributor(s) Lalonde S, Codina-Fauteux V, Méric de Bellefon S, Leblanc F, Beaudoin M, Dali R, Kwan T, Sin Lo K, Pastinen T, Lettre G
Citation(s) 31287004
Submission date Feb 06, 2019
Last update date Sep 24, 2019
Contact name Guillaume Lettre
Organization name Montreal Heart Institute
Street address 5000 Rue Bélanger
City Montreal
State/province Quebec
ZIP/Postal code H1T 1C8
Country Canada
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (4)
GSM3593256 HiC_teloHAEC_0h_r1
GSM3593257 HiC_teloHAEC_0h_r2
GSM3593258 HiC_teloHAEC_4h_r1
This SubSeries is part of SuperSeries:
GSE126200 Integrative vascular endothelial cell genomics identify AIDA as a coronary artery disease candidate gene
BioProject PRJNA521271
SRA SRP184300

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SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE126199_AtoB_comp_switch_merged.bed.gz 2.0 Kb (ftp)(http) BED
GSE126199_BtoA_comp_switch_merged.bed.gz 4.8 Kb (ftp)(http) BED
GSE126199_RAW.tar 34.8 Gb (http)(custom) TAR (of HIC) 907.8 Kb (ftp)(http) BW 908.2 Kb (ftp)(http) BW
GSE126199_teloHAEC_0h_merge.filt.intra.loop_counts.bedpe.gz 12.8 Mb (ftp)(http) BEDPE
GSE126199_teloHAEC_0h_merge_inter_30.hic 13.6 Gb (ftp)(http) HIC
GSE126199_teloHAEC_0h_merged_TADs_10kbres.500kbISS.200kbIDS_crane.bed.gz 22.3 Kb (ftp)(http) BED
GSE126199_teloHAEC_4h_merge.filt.intra.loop_counts.bedpe.gz 11.7 Mb (ftp)(http) BEDPE
GSE126199_teloHAEC_4h_merge_inter_30.hic 14.5 Gb (ftp)(http) HIC
GSE126199_teloHAEC_4h_merged_TADs_10kbres.500kbISS.200kbIDS_crane.bed.gz 21.9 Kb (ftp)(http) BED
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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