Chunk #60 — Materials and Methods — Meta-Analysis Gene-set Enrichment of variaNT Associations (MAGENTA) — Step 4: Gene set enrichment analysis of genome-wide association data
below). (iv) Finally, a nominal GSEA p-value, was calculated for each gene set gs, defined as the fraction of randomly sampled gene sets of identical set size, whose leading edge fraction is equivalent to or larger than the observed leading edge fraction of gene set gs. The null distribution of leading edge fractions was generated for each gene set gs by randomly sampling 10,000 gene sets from the genome (or more when <10−4) that are of identical set size to the effective size of gene set gs (after adjusting for physical clustering in the genome of subsets of genes in each randomly sampled gene set separately, as described above). Genes in gene set gs were not excluded from the random sampling procedure. (v) To correct for multiple hypothesis testing, Bonferroni correction was used (i.e. significance cutoff p = 0.05 divided by the number of hypotheses tested). This may be too stringent when a large number of gene sets is tested due to overlap of genes between the different gene sets.
