Demo run & demo data download
Demo run result URL
Download demo input data
- Schizophrenia GWAS SNP -log(P-value) data:
.txt
.gz
-
Schizophrenia gene association data:
.txt
.gz
Demo run: GWAS SNP P-value as demo input (schizophrenia)
The demo input is SNP P-value from the GWAS of schizophrenia (SZ) [1].
The P-value has been transformed to -log(P-value). With the default parameter of our i-GSEA4GWAS v2
server, 8 pathways were identified to be possibly associated with SZ with FDR < 0.25. Among these 8 pathways,
only one pathway is significantly enriched in deleterious and other variants seperately, while most of the pathways
were significantly enriched in eQTL and at least one ENCODE track, which is consistent with the recent view that most of GWAS
SNPs do not impact protein directly but affect other genes by regulatory function.
During these 8 pathways, 'antigen processing and presentation' is
statistically significant with FDR < 0.05.
There is a growing recognition that immune system dysfunction might play a pivotal role in the etiopathogenesis of schizophrenia [2].
The work of Craddock et al suggested that in schizophrenia, cellular mechanisms that are involved in antigen processing and
presentation could be less efficient [3].
Functional analysis based on Ensembl indicates that the LD-proxy (rs2072895) of rs1362126 in HLA-F is
annotated with deleterious; the LD-proxies (rs9260107 and rs9260118) of rs2860580 in HLA-A, LD-proxy
(rs2072895 and rs2844846) of rs1362126 in HLA-F and the LD-proxy (rs3100139) of rs2254835 in B2M are annotated
with splice region. The enrichment analysis for Ensembl other functional annotation in this pathway is
significant (P-value = 8.97×10-3).
Enrichment analysis based on eQTLs shows high significance (P-value = 3.78×10-103).
The enriched DNase-seq peaks, FAIRE peaks, TFBS peaks (SPP), TFBS peaks (PeakSeq) and Histone peaks
were mainly related with immune cells in blood, such as B-lymphocyte, Lymphoblastoid cell and B-cell.
Several brain related cell lines (SK-N-SH_RA and NH-A) and a fetal related cell line (Chorion) were also identified.
Reference
[1] Need, A.C., Ge, D., Weale, M.E., Maia, J., Feng, S., Heinzen, E.L., Shianna, K.V., Yoon, W., Kasperaviciute, D., Gennarelli, M. et al.
(2009) A genome-wide investigation of SNPs and CNVs in schizophrenia. PLoS Genet 5(2) e1000373
[2] Debnath, M., Cannon, D.M., Venkatasubramanian, G., (2012). Variation in the major histocompatibility complex [MHC] gene family in schizophrenia:
Associations and functional implications. Progress in neuro-psychopharmacology & biological psychiatry.
[3] Craddock, R.M., Lockstone, H.E., Rider, D.A., Wayland, M.T., Harris, L.J., McKenna, P.J. and Bahn, S. (2007) Altered T-cell function in schizophrenia: a cellular model to investigate molecular disease mechanisms. PLoS One 2(8) e692.
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