This is a set of Forge results generated by analysis of GWAS SNP sets obtained from the GWAS catalog (downloaded 28-03-2014). The examples are divided roughly into categories of phenotypes that have some broad similarity in terms of aetiology. Click on a thumbnail to be taken to the full PDF of the result. Note that with the switch to the binomial P value significance levels, some signals that were present using Z scores are only borderline trends now, and have been removed. Also these data use all SNPs from the GWAS catalog filtering for LD at r2 but without filtering for genome wide significance (5e-8). All analysis PDFs for GWAS catalog data downloaded on 03/09/2014 can be downloded from http://www.ebi.ac.uk/~dunham/All_results.pdf (LD filtered but all P values below 1e-5) and http://www.ebi.ac.uk/~dunham/All_results_p.pdf (LD filtered and P value filter at 5e-8).
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There is a clear enrichment pattern for overlap with hotspots in various myeloid and lymphoid (blood) tissues in the autoimmume diseases. The exact cells involved vary, in was that are compatible with the known differences in aetiologies for the specific diseases.
On the Roadmap Epigenome data, there is an enrichment signal for CD14 and CD34 cells. This is consistent with a role for macrophages in the aetiology.
For Celiac disease, the main enrichment in both datasets is with CD3, CD4 and CD8 cell samples, characteristic of the involvement of thymocuytes and subsequently T cells. The Roadmap Epigenome data also has a strong signal from thymus tissue itself supporting this. This is consistent with the T cell involvement in the disease since the extensive infiltration of CD8(+) T cells in the intestinal mucosa of celiac disease (CD) patients is a hallmark of the disease.
Crohn’s disease GWAS SNPs are enriched for overlap with T helper cells (Th2, CD3, CD4), NK cells (CD56) and some B cell (CD19) and Cytotoxic T cells or NK cells (CD8). The T cell involvement is reflected by a thymus enrichment. Notably there is signal from the small and large intestine and skin/fibroblast cells consistent with the site of inflammation and altered fibroblast function in the disease.
Again the T cell and thymus inflammatory enrichment is revealed, but now there is enrichment in muscle cells which is intriguing given the effects of neurological damage on muscle function in MS.
Rheumatoid Arthritis displays a slightly different pattern of enrichment in the blood cells. Although there is some enrichment in T cells (CD3, CD4 and CD8), thymus cell and CD34+ hematopoietic progenitor cells, the main enrichment is in CD19 B cells. CD19 cell depletion is the target of autoreactive plasma cells in Rheumatoid Arthritis. http://arthritis-research.com/content/14/S5/S1
In SLE an even more pronounced specific enrichment ifn CD19 cells is seen, reflecting the predominently B cell pathology of the disease with it’s anti-nucleic acid antibodies.
For Type 1 diabetes the autoimmune signature is not as strong although there is a suggestive T cell (CD3, CD4 and CD8) enrichment signal in the Roadmap data, consistent with the T cell invasion of the pancreatic iislets in Type 1.
Enrichment signal in fetal heart and fibroblasts. Maybe makes sense with blood vessle walls being involved.
There is a breast cancer line enrichment in the ENCODE data(MCF-7), but intriguingly various signals including a kidney signal in the Roadmap data.
Notably enrichment in prostate cancer cells but also Hela (cervical carcinoma) in ENCODE data.
Clear Fetal Lung enrichment in Pulmonary function (spirometry).
For decline note that muscle is more important than fetal lung pointing towards mechanism.
Not sure on the phenotype here (need to look up the study) but both fetal lung and muscle show enrichment along with fibroblasts.
Breathing is important when you are on dialysis, as well as fibroblast function.
This is a fibroblast related trait, and this shows in the enrichments.
Mostly Stomach and some Kidney important here.
Many tissues are important for height….
Again CD34 cells are enriched but there are also alternate B cell, monocytes and T cell blood enrichments and signals from spleen stomach and thymus tissue. The ENCODE data also has some signals from blood vessels, but some odd sporadic enrichments as well.
ENCODE data picks up a particular enrichment in blood vessels. The Roadmap data shows weak hear signal and fibroblasts.
The major enrichment is in fetal heart but in addition we see signal particularly from lung and muscle tissues plus some kidney.
For ventricular conduction the signal is from Fetal Heart and also from Fetal Muscle tissues.