We evaluated the statistical power for detecting an association of rs393152 with AD across the discovery (ADGC) and the combined, meta-analysis AD cohorts (ADGC + GERAD + deCODE + Oslo + CHARGE). Using a GWAS threshold of p < 5 × 10 −8 the power within ADGC was 0.028 and within the meta-analysis cohort was 0.36, demonstrating that even the combined cohort consisting of 21,289 AD cases and 51,263 controls was underpowered to detect an association between AD and rs393152 using a standard GWAS approach. However, leveraging PD such that power is computed conditional on discovery in the PD sample (stepwise gatekeeper hypothesis testing), by using p < 0.00625 (where Bonferroni corrected p = 0.05/number of genome-wide significant SNPs in PD), the power within ADGC was 0.854 and within the meta-analysis cohort was 0.998 indicating that restricting evaluation to only PD-significant SNPs results in considerable increase in statistical power for AD gene discovery. We also calculated the sample size needed to detect rs393152 ((C−1 Θ−1(5 × 10−8)2/ Θ−1(0.00625)2), where Θ−1 is the inverse standard normal cumulative distribution function) and found
