Failure to Validate Associations Between 12p13 Variants and Ischaemic Stroke, NEJM 2010; 362:1547-1550.
Recently published data from a meta-analysis of genomewide association studies showed that two common single-nucleotide polymorphisms (SNPs) near the NINJ2 and WNK1 genes on chromosome 12p13 were associated with ischaemic and, in particular, atherothrombotic strokes. To validate these results, we conducted a meta-analysis in a combined sample of 8637 cases and 8733 controls of European ancestry, as well as one population-based genomewide cohort study of 278 ischaemic strokes among 22,054 participants.
We found no association between rs12425791 and ischaemic stroke (odds ratio 0.97; 95% CI 0.91-1.04 p=0.41) or between rs11833579 and ischaemic stroke (odds ratio 1.02; 95% CI, 0.95 to 1.10; P = 0.55) in persons of European ancestry (Fig. 1). We found no association between either of the SNPs and atherothrombotic stroke in 2235 cases (P>0.10) and no association between either of the SNPs and incident ischemic stroke, recurrent ischemic stroke, and ischemic stroke subtypes (P>0.10 for all comparisons). The power to detect an association at an effect size below the lower limit of the 95% confidence interval surrounding the original estimate exceeded 99% for ischemic as well as atherothrombotic stroke.