i-GSEA4GWAS: a web server for identification of pathways/gene sets associated with traits by applying an improved gene set enrichment analysis to genome-wide association study

Zhang, Kunlin; Cui, Sijia; Chang, Suhua; Zhang, Liuyan; Wang, Jing

The second example data are SNP P-values of the GWAS of bipolar disorder, which is a case/control study and utilized the GeneChip 500K Mapping Array Set (Affymetrix chip) (2). i-GSEA4GWAS identified two pathways/gene sets (FDR < 0.05) by using the default '500 kb upstream and downstream of gene' SNPs-> genes mapping rule, searching 'canonical pathways' and GO terms, and masking the xMHC region. One pathway is 'glutathione metabolism' (FDR = 0.036), which was also reported by Holmans et al (30) . Reducing glutathione (GSH) level will lead to an increased potential for cellular oxidative stress, which has been implicated in the pathology of bipolar disorder, and recently some studies have been performed on animal models (31, 32) . The other one is 'cysteine type endopeptidase activity' (FDR = 0.041), which might be a novel functional biological mechanism related to bipolar disorder and worthy of further study. There is no pathway/gene set found with FDR < 0.05 or FDR < 0.25 by using GSEA with the same parameters.