Concerning the primary hypothesis, for each disorder, we obtained significant or highly significant evidence for an excess of associated genes at most thresholds. This supports the general validity of the gene-wide approach for detecting true association signals. However, it does not suggest that gene-wide tests make single locus tests redundant; rather that they are useful additional approaches. By way of illustration, we plot the rank order achieved by genes in the schizophrenia dataset (the figures for bipolar are similar) based upon uncorrected single SNP tests against that achieved with each of the gene-wide tests (Figure 1). As expected, the rank order of genes based upon the most significant uncorrected SNP correlates (Spearman r=0.8) with that obtained after correction for the number of independent SNPs in that gene (Figure 1a), but the correlation is much less (r=0.37) between the rankings achieved by the single SNP test and that obtained by the truncated-product approach (Figure 1b). Thus, the approaches are complementary in highlighting the likely involvement of specific genes although the relative merits of each in doing so necessarily awaits the reporting of many more confirmed associations.
