The most significant association was found on chromosome 20p12 with SNP rs2208454, located in intron 3 of MACRO Domain Containing 2 (MACROD2) gene and in the downstream region of Fibronectin Leucine Rich Transmembrane Protein 3 (FLRT3) gene. The OR for MRI-infarcts was 0.76 (95% CI=0.68–0.84, p=4.64×10−7). Additional adjustment for systolic blood pressure (OR=0.76, 95% CI=0.68–0.85) or hypertension (OR=0.76, 95% CI=0.68–0.84) did not change results. Figure 2 shows a forest plot of risk estimates for rs2208454 across the 7 cohorts. Twenty-two other SNPs in intron 3 of MACROD2 were also associated with MRI-infarcts with a p-value of less than 1.0×10−5 (Table 2 and Appendix, Table A). All were in linkage disequilibrium with rs2208454: r2>0.64 for all and r2>0.8 for 17 of the SNPs. Of these 22 SNPs, 1 was intronic within FLRT3 (rs6110247), and 3 were potential transcription factor binding sites (rs6110247, rs743216, and rs3789335). Figure 3 shows all SNPs within a 200kb region on either side of the top hit, together with p-values, recombination rates, and known genes in that region.
