There are several indications that the detected pleiotropy within chromosome 17 represents biological signal and not analysis artifacts or type 1 error. First, the use of APOE co-varied SNPs from the ADGC minimizes concerns that the detected SNPs represent spurious association resulting from the known large effect of APOE on AD risk (for an example of this, see reference 28). Importantly, our findings indicate the presence of genetic signal independent of the chromosome 19 APOE cluster. Second, rs393152 was significantly associated with AD risk in three independent AD replication cohorts and demonstrated equivalent effect sizes in all five AD cohorts. Third, the identified pleiotropic locus was in r2 LD > 0.8 with a number of variants within the tau-encoding MAPT gene on 17q21 indicating that the detected signal was specific to the MAPT region. Fourth, the leading AD-associated SNP in the MAPT region (rs1981997, r2 LD = 1.0 with rs393152 in the HapMap 2) demonstrated a similar meta-analysis p-value to rs393152 providing further evidence that our AD/PD pleotropic SNP was not a false positive result. Finally, the A allele of
