A meta-analysis of genomewide association studies (GWAS) did not validate findings that associated the single-nucleotide polymorphisms rs12425791 and rs11833579 with stroke. Representing the members of the International Stroke Genetics Consortium, Jonathan Rosand, MD, MSc, Massachusetts General Hospital, Boston, MA, detailed findings from this meta-analysis.

A previous GWAS found that two intergenic single-nucleotide polymorphisms (SNPs), rs12425791 and rs11833579, on chromosome 12p13 and within 11 kb of the NINJ2 gene were associated with stroke [Ikram MA et al. N Engl J Med 2009]. The International Stroke Genetics Consortium set out to validate these results in a meta-analysis that was conducted using a combined sample of 8637 cases and 8733 controls of European ancestry and one population-based genomewide cohort study of 278 ischemic strokes among 22,054 subjects. Investigators evaluated associations between the two SNPs and ischemic stroke, incident stroke, and stroke subtypes (according to Trial of ORG 10172 in Acute Stroke Treatment [TOAST] criteria). Similar analyses were performed in cases and controls of African-American, Pakistani, and Chinese ancestry.

This well-powered meta-analysis detected no association between rs12425791 or rs11833579 and ischemic stroke in the cohort of European ancestry (OR, 0.97; 95% CI, 0.91 to 1.04; p=0.41 and OR, 1.02; 95% CI, 0.95 to 1.10; p=0.55, respectively). Additionally, no association was found for atherothrombotic stroke, incident ischemic stroke, recurrent ischemic stroke, or any of the ischemic stroke subtypes with regard to either SNP, according to 2235 cases (p>0.10 for all stroke categories). The original meta-analysis reported significant heterogeneity (rs11833579: heterogeneity p=0.073, l2=56.1%; rs12425791: p=0.15, l2=42.1%). However, no significant heterogeneity was observed in the current meta-analysis by the consortium (heterogeneity p>0.20; l2<20%).

Based on these results, members of the International Stroke Genetics Consortium concluded that these SNPs were not associated with increased risk for ischemic stroke.