First, we attempted to determine the evidence for association for the six loci reported previously from GWAS to be associated with ischaemic stroke (HDAC9, PITX2, ZFHX3, NINJ2, PRKCH, and 9p21).8, 9, 10, 11, 12, 14 After determining the evidence for association with the previously reported SNPs, we investigated whether any proxy SNPs were more significantly associated in the METASTROKE dataset. Because some loci had been identified in discovery populations included in METASTROKE, we initially did analyses for the whole dataset, and then we restricted analysis to the lead SNP for every locus in the METASTROKE cohorts that had not been included in the discovery phase of the initial publication. We set the significance level for independent replication at p<0·01, corresponding to Bonferroni corrected type 1 error <5% for the five SNPs (excluding PRKCH) tested.
