Aside from differences between methods, Table 3 also shows a clear difference between self-contained and competitive gene-set analysis. This is not a difference in power, but rather a difference of null hypothesis. Competitive tests attempt to correct for the baseline level of association present in the data and accordingly have a much more general null hypothesis. The impact of this difference in hypothesis can be illustrated by comparing the MAGMA self-contained and competitive analyses, since they are performed in the same framework. Whereas the self-contained analysis detects 39 gene sets that show association with the phenotype, the competitive analysis detects only one of those 39. For the remaining 38 gene sets, there is no evidence in the data that the associations in those gene sets are any stronger than would be expected by chance given the polygenic nature of CD. The gene-set that remains is the Regulation of AMPK via LKB1 (REACTOME) set. For two additional gene sets, Cell Adhesion Molecules (KEGG) and ECM-receptor Interaction (KEGG), the competitive p-value also drops below the significance threshold (Table 4 and S12 Fig)
