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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 (SNP-->gene mapping rule: 20kb upstream/downstream, gene sets: KEGG, BioCarta and GO, LD data: 1000 Genomes EUR), 19 pathways were identified to be significantly associated with SZ with FDR < 0.05. Among these 19 pathways, one ('antigen processing and presentation') was significantly enriched in Ensembl other putative functional sites, 8 of them were significantly enriched in at least one track of ENCODE regulatory elements, and 14 of them were significantly enriched in eQTL, which indicated most SNPs in these pathways were in non-coding regions which may regulate the gene expression.

For 'antigen processing and presentation', it is suggested that in schizophrenia, cellular mechanisms that are involved in antigen processing and presentation could be less efficient [2]. Functional analysis for the significant SNPs and their LD proxies in this pathway indicates that LD-proxies (rs9260107 and rs9260118) of rs2860580 in HLA-A, LD-proxies (rs2072895 and rs2844846) of rs1362126 in HLA-F and LD-proxy (rs3100139) of rs2254835 in B2M are annotated as splice region; LD-proxy (rs2072895) of rs1362126 in HLA-F is annotated as deleterious. The three genes are all related with major histocompatibility complex (MHC) class I molecules, which is consistent with the recent findings about the contribution of MHC region site to schizophrenia [3]. Four SZ-associated pathways 'potassium ion transport', 'regulation of heart contraction', 'voltage gated potassium channel complex' and 'potassium channel activity' were enriched in ENCODE FARE track "wgEncodeOpenChromFaireMedulloPk" (a cell line of brain), indicating most SNPs in these pathways may regulate the gene expression in brain. These functional SNPs and genes we identified may lead important function in schizophrenia and deserve further validation.

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] 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.
[3] Ripke S, O'Dushlaine C, Chambert K, Moran JL, Kahler AK, et al. (2013) Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nat Genet 45: 1150-1159.





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Last update: May 14, 2014