Genome-wide identification of m⁶A-associated single nucleotide polymorphisms in complex diseases of nervous system

N6-methyladenosine (m⁶A) is one of the most abundant chemical modifications on RNA and can affect the occurrence and development of diseases. Some studies have shown that the expressions of some m⁶A-related genes are significantly regulated by single nucleotide variants (SNV). However, the function of m⁶A-associated single nucleotide polymorphisms (m⁶A-SNP) remains unclear in multiple sclerosis (MS), Alzheimer's disease (AD) and Parkinson's disease (PD). Here, we identified the disease-associated m⁶A-SNPs by integrating genome-wide association study (GWAS) and m⁶A-SNPs from the RMVar database, and confirmed the relationship between these identified m⁶A-SNPs and their target genes in eQTL analysis and gene differential expression analysis. Finally, 26 genes corresponding to 20 m⁶A-SNPs with eQTL signals were identified and differentially expressed (P < 0.05) in MS, 15 genes corresponding to 12 m⁶A-SNPs (P < 1e-04) were differentially expressed in AD, and 27 PD-associated m⁶A-SNPs that regulated the expression of 31 genes were identified. There were 5 HLA genes with eQTL signals (HLA-DQB1, HLA-DRB1, HLA-DQA1, HLA-DQA2 and HLA-DQB1-AS1) to be detected in the three diseases. In summary, our study provided new insights into understanding the potential roles of these m⁶A-SNPs in disease pathogenesis as well as therapeutic target.