Genome-wide detection of m6A-associated SNPs in atrial fibrillation pathogenesis

Abstract

Objective: N6-Methyladenosine (m6A) modification is of great importance in both the pathological conditions and physiological process. The m6A single nucleotide polymorphisms (SNPs) are associated with cardiovascular diseases including coronary artery disease, heart failure. However, it is unclear whether m6A-SNPs are involved in atrial fibrillation (AF). Here, we aimed to explore the relationship between m6A-SNPs and AF. Method: The relationship between m6A-SNPs and AF was evaluated by analyzing the AF genome-wide association study (GWAS) and m6A-SNPs annotated by the m6AVar database. Further, eQTL and gene differential expression analysis were performed to confirm the association between these identified m6A-SNPs and their target genes in the development of AF. Moreover, we did the GO enrichment analysis to figure out the potential functions of these m6A-SNPs affected genes. Result: Totally, 105 m6A-SNPs were identified to be significantly associated with AF (FDR < 0.05), among which 7 showed significant eQTL signals on local genes in the atrial appendage. By using four public AF gene expression datasets, we identified genes SYNE2, USP36, and THAP9 containing SNPs rs35648226, rs900349, and rs1047564 were differentially expressed in AF population. Further, SNPs rs35648226 and rs1047564 are potentially associated with AF by affecting m6A modification and both of them might have an interaction with RNA-binding protein, PABPC1. Conclusion: In summary, we identified m6A-SNPs associated with AF. Our study provided new insights into AF development as well as AF therapeutic target.