We conducted a fixed-effects meta-analysis of results from the 6 studies, with 7 cohorts counting the Rotterdam Study II, using inverse-variance weighting. After QC, filtering, and imputation within each study, we restricted our meta-analysis to 2,217,889 autosomal SNPs that were common to all studies and had an average minor allele frequency (MAF) greater than 2%. Details on the meta-analysis strategy and functional annotation of SNPs are available in the Appendix, Section 5. As suggested by others,6 we decided a priori on a genome-wide significance threshold of 5×10−8. SNPs with 5×10−8<p<1×10−5 were considered highly suggestive associations. As available in meta-analysis, we also examined associations with candidate SNPs, or their proxies, previously reported to be significantly associated with covert MRI-infarcts.
