The traditional strategy for GWAS studies tests one SNP at a time. Although widely used, single-SNP GWAS analysis does not have adequate power to detect SNPs that have marginally weak, but jointly strong genetic effects. Jointly analyzing SNPs within the same biological pathway simultaneously complements the single-SNP analysis and can reveal new insights to the understanding of complex human traits. Our SNP set enrichment analysis operates on representative SNPs of genes and then combines the effects of SNPs within the same pathway by a weighted Kolmogorov-Smirnov running sum statistic test [22]. This strategy has the potential to increase the chance of identifying genetic variants that that individually have a modest risk.
