The discovery meta-analysis confirmed associations at genome-wide significance levels for HDAC9 with large-vessel disease, and for both PITX2 and ZFHX3 with cardioembolic stroke (table 2). For PITX2, ZFHX3, and HDAC9 a proxy SNP was more significant in the METASTROKE dataset than the SNP from the original publication (original SNP shown in appendix). The 9p21 locus was associated with large-vessel disease with a similar OR (1·15, 95% CI 1·08–1·23, in METASTROKE) to that reported previously (1·21, 1·07–1·37),10 although it did not reach genome-wide significance (p=3·32×10−5). All four associations were subtype specific, being present only for a single stroke subtype (table 2). To determine the extent to which these results replicated the findings from the originally published associations, we repeated the meta-analysis, this time excluding the populations that contributed to the discovery phase of the original publication. For the PITX2, ZFHX3, HDAC9, and 9p21 loci, the associations were replicated in the independent METASTROKE samples (table 2). The population attributable risks in the METASTROKE discovery cohort were estimated as 5·8% for PITX2 and 7·0% for ZFHX3 in cardioembolic stroke, and 4·5% for HDAC9
