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| Status |
Public on Aug 09, 2018 |
| Title |
Genetic regulatory mechanisms of smooth muscle cells map to coronary artery disease risk loci |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Coronary artery disease (CAD) is the leading cause of death globally. Genome-wide association studies (GWAS) have identified more than 130 independent loci that influence CAD risk, most of which reside in non-coding regions of the genome. To interpret these loci, we generated transcriptome and whole-genome datasets using human coronary artery smooth muscle cells (HCASMC) from 52 unrelated donors, as well as ATAC-seq epigenomic datasets on a subset of 8 donors. Through systematic comparison with publicly available datasets from GTEx and ENCODE projects, we identify transcriptomic, epigenetic, and genetic regulatory mechanisms specific to HCASMC. We validate the relevance of HCASMC to CAD risk using transcriptomic and epigenomic level analyses. By jointly modeling eQTL and GWAS datasets, we identified five genes (SIPA1, TCF21, SMAD3, FES, and PDGFRA) that modulate CAD risk through HCASMC, all of which have biologically relevant functional roles in vascular remodeling. Comparison with GTEx data suggests that SIPA1 appears to influence CAD risk predominantly through HCASMC, while other annotated genes may have multiple cell targets. Together, these results provide new biological insights into the regulation of a critical vascular cell type associated with CAD in human populations.
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| Overall design |
RNA-Seq and ATAC-seq on 52 lines of human coronary artery smooth muscle cells
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| Contributor(s) |
Liu B, Nguyen T, Castano V, Wang T, Nurnberg S, Pjanic M, Rader DJ, Montgomery SB, Miller CL |
| Citation(s) |
30146127 |
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| Submission date |
Apr 18, 2018 |
| Last update date |
Sep 19, 2019 |
| Contact name |
Thomas Quertermous |
| E-mail(s) |
[email protected]
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| Phone |
650-723-5012
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| Organization name |
Stanford University
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| Department |
Medicine Cardiology
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| Lab |
Quertermous
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| Street address |
300 Pasteur Drive
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| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| Country |
USA |
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| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (60)
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| Relations |
| BioProject |
PRJNA451517 |
| SRA |
SRP142360 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE113348_RAW.tar |
48.4 Mb |
(http)(custom) |
TAR (of NARROWPEAK) |
| GSE113348_rnaseqc.hcasmc_eqtl.reads.gct.gz |
2.7 Mb |
(ftp)(http) |
GCT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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