Gene set enrichment analysis using Wilcoxon tests

Gene set enrichment analysis (GSEA) is typically based on tests derived from the KolmogorovSmirnov, which is underpowered and a need for simpler methods has been identified.[2] The wgsea package contains functions for conducting GSEA using a Wilcoxon test to test for differences in the distribution of p values between SNPs within the gene set under test and a control set of SNPs. The mean of the Wilcoxon test statistic is unperturbed by correlation between the SNPs resulting from linkage disequilibrium, but its variance is. We use permutation of the case control status to generate Wilcoxon statistics under the null. This permutation preserves the correlation structure, and because we are only trying to estimate the variance rather than a permutation p value we need only a modest number of permutations. This vignette steps through analysis of an example dataset. For further detail, and example of an application to real data, please see [1].