Integrative Analysis Identified and as Potential Causal Genes for Ischemic Stroke.

To highlight potential functional variants and causal genes for ischemic stroke (IS) in genomic loci identified by genome-wide association studies (GWAS). We examined the association between mA-SNPs and IS in large scale GWAS. Furthermore, eQTL analysis was performed to evaluate the effect of mA-SNPs on gene expression. The top associations between mA-SNPs and gene expressions were validated in 40 individuals from the Chinese Han population. Besides, we applied differential expression analysis and Mendelian randomization (MR) analysis to detect potential causal genes for IS. We found 310 (7.39%) mA-SNPs which were nominally associated with IS. The proportion of mA-SNPs with < 0.05 for IS was significantly higher than the non-mA-SNPs (95%CI: [5.84%, 7.36%], = 0.02). We found that the IS-associated mA-SNP rs2013162 was associated with expression ( = 6.30 × 10), meanwhile was differentially expressed between IS cases and controls ( = 6.15 × 10) and showed a causal association with IS ( = 3.64 × 10). Similar results were found for mA-SNP rs2273235 in the gene which was associated with cardioembolic stroke ( = 8.47 × 10). The associations of rs2013162 and rs2273235 with the expression of and were validated in blood cells ( = 0.0247 and 0.0007), respectively. This study showed that mA-SNPs may affect IS risk through altering gene expressions. The results suggested that mA might play a role in IS etiology and gene expressions that affected by mA may be causal factors for IS.