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

To overcome these limitations, the principle of gene set analysis (GSA), which was recently developed to facilitate handling of genome-wide expression data (4) , has been introduced to GWAS. GSA tests the correlation between gene set, which is defined as genes involved in the same pathway, and trait, resting on the assumption that genes belonging to a disease-related pathway/gene set trend to reveal concordant signals. Recently, several implementations or application programs using the GSA principle have been developed (3, (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) . An interesting implementation is the gene set enrichment analysis (GSEA) which technically evaluates whether the distribution of genes sharing a biochemical or cellular function is different from the distribution of a ranked genome-wide gene list by computing Kolmogorov-Smirnov like statistics (3, 15) . Successful applications of GSEA in GWAS include the study of Parkinson's disease (3), Crohn's disease (11) and the study of host control for HIV-1 (9) .