These results indicate that leveraging the genetic signal in one phenotype may improve statistical power for gene discovery in a second, related phenotype. Rather than evaluating all possible AD susceptibility loci, we restricted our analyses to only those 8 SNPs that were below genome-wide threshold in PD. As such, detection of AD susceptibility loci only among genome-wide significant PD susceptibility loci obviates the need for applying a p < 5 × 10 −8 threshold and constitutes stepwise gatekeeper hypothesis testing. 17 This two-stage stepwise gatekeeper framework is conceptually similar to the ‘proxy-phenotype’ method, which has recently been utilized to identify common variants associated with cognitive performance. 24 It is important to note that this approach does not lower the statistical ‘bar’ for gene discovery and maintains a constant Type I error rate. By exploiting statistical power from PD, we were able to identify one SNP within the CRHR1 locus on chromosome 17 (meta-analysis p-value = 1.65 × 10−7, OR = 0.91, 95% CI = 0.88–0.94) that was significantly associated with increased AD risk. Importantly, use of this stepwise, pleiotropic approach,
