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| Status |
Public on Sep 01, 2020 |
| Title |
An integrative multiomic network model links the canonical lipid metabolism pathway to glucose regulation in coronary artery disease |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Elevated plasma cholesterol and Type 2 Diabetes (T2D) are associated with Coronary Artery Disease (CAD). Individuals treated with cholesterol-lowering statins have increased T2D risk, while individuals with hypercholesterolemia have reduced T2D risk. We explored the relationship between lipid and glucose control by constructing network models from the STARNET study with sequencing data from seven cardiometabolic tissues obtained from CAD patients during coronary artery by-pass grafting surgery. By integrating gene expression, genotype, metabolomic and clinical data, we identified a Glucose and Lipid Determining (GLD) regulatory network showing inverse relationships with lipid and glucose traits. Master regulators of the GLD network also impacted lipid and glucose levels in inverse directions. Experimental knockdown of one of the GLD network master regulators, Lanosterol Synthase (LSS), in mouse confirmed the inverse relationships to glucose and lipid levels as predicted by our model and provided mechanistic insights.
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| Overall design |
RNAseq data from 6 mice fed BIBB-515 and 6 mice fed a control diet
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| Contributor(s) |
Cohain AT, Barrington WT, Jordan DM, Beckmann ND, Argmann CA, Houten SM, Charney AW, Ermel R, Sukhavasi K, Franzen O, Koplev S, Whatling C, Belbin GM, Yang J, Hao K, Kenny EE, Tu Z, Zhu J, Gan L, Do R, Giannarelli C, Kovacic JC, Ruusalepp A, Lusis AJ, Bjorkegren JL, Schadt EE |
| Citation(s) |
33483510 |
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| Submission date |
Aug 31, 2020 |
| Last update date |
Jan 26, 2021 |
| Contact name |
Daniel Michael Jordan |
| E-mail(s) |
daniel.jordan1@mssm.edu
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| Organization name |
Icahn School of Medicine at Mount Sinai
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| Department |
Genetics and Genomic Sciences
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| Street address |
1 Gustave L Levy Place, box 1498
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10029 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA660471 |
| SRA |
SRP279499 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE157223_RAW.tar |
104.8 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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