This meta-analysis of GWAS data on covert MRI-defined brain infarcts included 9401 participants without a history of transient ischemic attack or stroke from 6 community-based studies. The most significant association (p=4.64×10−7) was found for SNP rs2208454 on chromosome 20p12, located in intron 3 of MACROD2 and in the downstream region of FLRT3. The less common allele was associated with a lower risk. Twenty-two SNPs in linkage disequilibrium with rs2208454 were also associated with MRI-infarcts with p-values less than 1.0×10−5, as were 28 other SNPs in 8 different loci. No association reached our preset threshold for genome-wide significance of 5.0×10−8. In 2 replication samples of 1822 white participants from 3C-Dijon and 644 African-American participants from ARIC, we did not observe an association with rs2208454, although 4 SNPs within 200kb from rs2208454 were associated with MRI-infarcts in the African-American sample. Finally, we failed to observe an association with SNPs previously reported to be associated significantly with covert MRI-infarcts in candidate genes studies.
