To this end, we compared Pascal with the methods based on the hypergeometric test (using 9 different threshold values) and the rank-sum test proposed by Segrè et al.[3] for 118 GWAS (S1 Table). All GWAS were derived from European populations justifying the use of the European 1KG genotypes as reference population. For a given GWAS, we asked how many tested pathways reached genome-wide significance at the Bonferroni-corrected p-value threshold of 0.05. Our results indicate that globally our approach has higher power than either the methods using the hypergeometric test (across all tested thresholds), or the rank-sum test (Figs 5A and S6). For individual traits (Fig 5B), specific choices of the threshold parameter of the hypergeometric test sometimes reveal more pathways, but again the value of the optimal threshold varies across traits and cannot be known a priori.
