Although MAGMA showed better power than other tools for both the self-contained and competitive gene-set analysis, these comparisons also revealed considerable differences between the methods. This was most pronounced for the competitive gene-set analysis, with even results for individual methods showing significant variability based on the choice of cut-off. At present no comprehensive evaluation of the differences between existing gene-set analysis methods exists, leaving the causes and implications of these difference unclear. It is beyond the scope of this paper to perform such an evaluation, but the degree of discordance between most methods strongly suggests a need for future research in this direction. An additional caveat is that it is unknown to what extent the observed differences in power between methods may depend on the specific genetic architecture of Crohn’s diseases, and as such generalizing the results to other genetic architectures must be done with caution.
