The type 1 error rates for the gene-set analysis were also found to be well controlled for both the self-contained and competitive test (Table S2 in S2 File). For the competitive test an additional simulation using a polygenic null model was performed, with effects explaining a combined 50% of the phenotypic variance assigned to randomly selected SNPs. This polygenic type 1 error rate was also well controlled. The type 1 error rates for the self-contained analysis under the polygenic null model are also shown. These are considerably inflated because self-contained gene-set analysis by its definition is not designed to correct for polygenicity, illustrating the risk of performing self-contained analysis on polygenic phenotypes.
