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Chunk #29 — Results

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Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis of genome-wide association studies.
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We selected a total of 12 novel SNPs for testing in the independent replication cohort: three associated with all ischaemic stroke, five associated with specific stroke subtypes, and two each associated with young stroke and female stroke. Four of these SNPs showed associations close to genome-wide significance in the discovery cohort: rs225132 in the ERRF11 gene and rs17696736 in the NAA25 (C12orf30) gene with all ischaemic stroke (p=6·3×10−8 and 5·9×10−8, respectively), rs7937106 in ALKBH8 with large-vessel disease (p=5·9×10−8), and rs13407662 on chromosome 2p16.2 (p=5·2×10−8) in an intergenic region with small-vessel disease. The remaining SNPs were identified at the suggestive significance level of p<5×10−6. Table 3 shows details of these SNPs, including stroke subtypes with which they were associated, and significance levels. These 12 novel SNPs were taken forward for replication in an additional 13 347 cases and 29 083 controls. Figure 3 shows the plots of –log10(p values) by chromosomal location for the analysis of all stroke and the three main subtypes.Table 3Association signals for SNPs selecting for testing in the independent replication cohort by subtypeChrSNPCandidate geneRARAFpdiscovery; ORdiscovery(95% CI)All replication