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, where power is computed conditional on discovery in the PD sample, resulted in considerable improvement in statistical power for AD gene detection. In contrast, using a standard GWAS approach, neither the discovery ADGC cohort nor the combined meta-analysis cohort were sufficiently powered to detect rs393152. Given the comparable sample sizes with our current study, it is likely that the original AD GWASs 12–13, 25–26 and even the recent meta-analysis (stage 1) 27 were underpowered to detect MAPT-associated signal in AD.
