Genome-Wide Detection of m⁶A-Associated Genetic Polymorphisms Associated with Ischemic Stroke

N⁶-Methyladenosine (m⁶A) methylation is the most abundant post-transcription modification in eukaryotes and plays a vital role in many pathological conditions including cerebral ischemia-reperfusion injury and vascular inflammation. Moreover, recent studies have reported that single-nucleotide polymorphisms (SNPs) can affect the m⁶A modification. Therefore, we investigated the relationship between m⁶A-SNPs and ischemic stroke (IS) risk through integrative analysis of an IS genome-wide association study and m⁶A-SNP list from the m6AVar database. Next, we performed eQTL and differential expression analysis to support these IS-associated m⁶A-SNPs. Finally, using the identified polymorphisms, a PPI network was constructed using the STRING database, and GO and pathway enrichment analyses were performed using the DAVID online tool. Accordingly, we identified 305 IS-associated SNPs that could affect m⁶A methylation. Next, 158 of these SNPs were determined to have eQTL signals on local genes. We further identified 84 local genes (containing a total of 87 SNPs) that were differentially expressed in IS patients. Finally, we identified several biological processes and pathways related to IS pathogenesis, such as "leukocyte migration" and "focal adhesion." In summary, our study detected dozens of m⁶A-SNPs as critical functional polymorphisms and novel genetic biomarkers for IS susceptibility and provided a new means of elucidating the biological mechanism underlying IS development.