Chunk #61 — Materials and Methods — Meta-Analysis Gene-set Enrichment of variaNT Associations (MAGENTA) — Step 4: Gene set enrichment analysis of genome-wide association data
To test the robustness of our GSEA results for the mitochondria-related gene sets, we applied an alternative GSEA statistical test, based on a one-tailed Mann-Whitney rank-sum test (Table S13). First, for each gene set gs we calculated a one-tailed rank-sum p-value that tests the alternative hypothesis that ranks for all genes in gene set gs are skewed towards high ranks compared to the gene score ranks of the rest of the genes in the genome. Second, a similar one-tailed rank sum p-value was calculated for 10,000 random gene sets of identical size that were randomly sampled from the genome and adjusted for chromosome clustering of subsets of genes in the gene set. Finally, a rank-sum based GSEA p-value, was computed for gene set gs as the fraction of randomly sampled gene sets whose rank-sum p-value was equivalent to or more significant than the rank-sum p-value of the tested gene set gs.
