To perform SNP-based pathway enrichment analysis of GWAS data, we developed a JAVA based software package called SNP Set Enrichment Analysis (SSEA) by extending the original GSEA code. SSEA consists of four procedures as outlined in Figure 1: 1) calculating the P-value of the association of each SNP to a trait of interest, 2) selecting representative SNPs for each gene using an adaptive SNP combination method, calculating the average number of representative SNPs for genes in each pathway and reselecting SNPs for gene in each pathway, 3) ranking all selected SNPs by their P-values and testing if the SNPs from a pathway are enriched with high ranks, and 4) calculating the FDR of the discovered pathways. See Methods for details.
