and genes with large number of SNPs, as larger pathways are expected to show more significant genes or SNPs just by chance. We checked several potential factors that might affect pathway significance: pathway size, gene size, total bp content, and average content. We found these factors are uncorrelated with pathway significance (Supplementary Figure 1a,b,c,d in Additional file 1), confirming that using multiple representative SNPs per gene and permutations are able to reduce the bias introduced by gene and pathway sizes.