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| Status |
Public on Nov 13, 2016 |
| Title |
Integrative Epigenome-Wide Analysis Shows That DNA Methylation May Mediate Genetic Risk In Inflammatory Bowel Disease [Cells, Methylation profiling] |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Epigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2, TXK) in an independent cohort.
Using paired genetic and epigenetic data, we delineate methylation quantitative trait loci; VMP1/microRNA-21 methylation associates with two genetic polymorphisms in linkage disequilibrium with a known IBD susceptibility variant. Separated cell data highlight the cell type of origin of epigenetic signals seen in whole blood; IBD-associated hypermethylation within the TXK gene transcription start-sitepromoter region negatively correlates with gene expression in whole blood and CD8+ T-cells, but not other cell types. Thus, site-specific DNA methylation changes in IBD are relatedrelate to underlying genotype and associate with cell-specific alteration in gene expression.
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| Overall design |
DNA methylation profiling using the Illumina450K array in whole blood and separated cells (CD14+ monocytes, CD4+ and CD8+ T-cells, naive CD4+ T Cells) in inflammatory bowel disease cases and controls
Several samples were excluded during sample processing (e.g. sex mismatches, mislabelled samples, technical replicates). The following samples were excluded in the final analysis (P009034-16122013-TD8-01, P009034-16122013-TDM-01, P009034-16122013-TD4-01, P008985-09102013-TDM-01, P007821-10102013-TDM-01, P007821-10102013-TD8-01, P008946-28082013-TDM-01). The following technical replicates were also excluded from final analysis (P009050-10012014-TB-01_R2, P009050-10012014-TB-01_R3, P009050-10012014-TB-01_R4)
Simplified_Diagnosis: CD=Crohn's disease, UC=Ulcerative colitis, HC=Control
Full_Diagnosis: CD=Crohn's disease, UC=Ulcerative colitis, HL=Healthy Lab Control, IB = Symptomatic Control
Cell Type: wh blood = whole blood, monocytes = CD14+ monocytes, CD4= CD4+ T-Cell, CD8 = CD8+ T-Cell
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| Contributor(s) |
Ventham N, Satsangi J |
| Citation(s) |
27886173 |
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| Submission date |
Oct 05, 2016 |
| Last update date |
Mar 22, 2019 |
| Contact name |
Nichols Ventham |
| E-mail(s) |
nicholas.ventham@ed.ac.uk
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| Organization name |
Univerisity of Edinburgh
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| Department |
CGEM
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| Lab |
Gastrointestinal Unit
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| Street address |
Western General Hospital
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| City |
Edinburgh |
| ZIP/Postal code |
EH4 6XU |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (240)
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| This SubSeries is part of SuperSeries: |
| GSE87650 |
Integrative Epigenome-Wide Analysis Shows That DNA Methylation May Mediate Genetic Risk In Inflammatory Bowel Disease |
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| Relations |
| BioProject |
PRJNA345595 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE87640_RAW.tar |
2.1 Gb |
(http)(custom) |
TAR (of IDAT) |
| GSE87640_UnprocessedMethCells450kSignalIntensities.txt.gz |
552.7 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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