This meta-analysis has strengths. It included 6 large cohort studies with similar MRI protocols. The analyses were restricted to white participants to minimize the risk of population stratification. Genotyping was subjected to rigorous quality control. Our study also has limitations. Despite having close to 10,000 participants of whom almost 2,000 had covert MRI-infarcts, we had limited power to detect associations with small effect sizes and associations with rare variants. An important caution is that the association with the top SNP was not directly replicated in 2 independent samples. Hence we cannot exclude the possibility that this association was a chance finding. However, the power to detect an association with rs2208454 in the 2 replication samples was relatively low: 61% for the white participants from 3C-Dijon and 18% for the African-American participants from ARIC, assuming the same effect size as in the discovery sample, which is likely an overestimation.28 The definition of infarcts may also have differed across discovery and replication cohorts, especially concerning the discrimination of infarcts from enlarged perivascular spaces. Furthermore, identified SNPs may not be the causal variants
