Objectives: Replication of GWAS association findings remains the gold standard for results validation. Our aim was to test the association of four polymorphisms (rs1671021 in LLGL2, rs753307 in RUVBL2, rs6007897 and rs4044210 in CELSR1) previously identified as ischemic stroke (IS) risk factors in a phased GWAS performed on 6341 Japanese individuals [1].
Methods: These polymorphisms were genotyped in a Portuguese sample of 566 IS cases and 525 controls, and their allele, genotype and haplotype associations were assessed.
Results: rs6007897 and rs4044210 in CELSR1 were associated with stroke risk individually (OR[95%CI]=1.43[1.13-1.81], p=0.003 and 1.38[1.09-1.74], p=0.007, respectively), and in combination as a haplotype. These associations remain after correction for multiple testing and in a meta-analysis with the original findings. The other polymorphisms were not associated.
Conclusions: Our study independently confirmed for the first time the association between IS and CELSR1. This finding and the mechanisms by which these genetic variants exert their effects on stroke pathogenesis warrant further replication and investigation.
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