Analysis of pathways can be done in two different ways. One way is to use the pathway as a group, and run the test on the entire pathway. On the other hand, for large pathways, it may be beneficial to use a method that allows a gene with a strong signal to have a high impact on the combined pathway test-statistic (T). If a pathway contains G non-overlapping genes, a method to do this is to use the weighted-sum method on each gene, and combine the resulting p-values (π 1,…,πG) with the Fisher product test statisticSince π 1,…,πG are i.i.d. uniformly(0,1) distributed under the null-hypothesis, T is χ2-distributed with 2G degrees of freedom, and can be evaluated accordingly [42],[43]. This method allows for fast analysis of different pathways, using the results from the gene-analysis, and can thereby assist in the functional analysis of a disease association study.
