i-GSEA4GWAS

i-GSEA4GWAS performs improved gene set enrichment analysis on GWAS SNP P-values to identify pathways and gene sets associated with complex traits.

Key Features:

• i-GSEA adaptation: Implements an improved gene set enrichment analysis (i-GSEA) specifically adapted for GWAS data.
• Permutation of SNP labels: Uses permutation of SNP labels to assess enrichment significance.
• Summary-statistic input: Performs enrichment analysis using only a list of GWAS SNP P-values without requiring genotype data.
• Pathway prioritization: Prioritizes pathways and gene sets that contain a high proportion of significant genes.
• Aggregation of weak signals: Detects collective impacts of less significant SNPs that are often overlooked by single-SNP analyses.

Scientific Applications:

• Pathway and gene-set discovery: Identifies biological pathways and gene sets associated with complex traits from GWAS summary statistics.
• Systems-level interpretation: Reveals biological functions and mechanisms by aggregating SNP-level signals into gene sets and pathways.
• GWAS result interpretation: Supports exploratory and hypothesis-driven analyses for interpreting genetic contributions to complex diseases.

Methodology:

Applies an improved gene set enrichment analysis (i-GSEA) adapted for GWAS, performing permutation of SNP labels to compute enrichment using only GWAS SNP P-values and prioritizing pathways/gene sets with a high proportion of significant genes.