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

N6-methyladenosine (mA) 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 mA-related genes are significantly regulated by single nucleotide variants (SNV). However, the function of mA-associated single nucleotide polymorphisms (mA-SNP) remains unclear in multiple sclerosis (MS), Alzheimer's disease (AD) and Parkinson's disease (PD). Here, we identified the disease-associated mA-SNPs by integrating genome-wide association study (GWAS) and mA-SNPs from the RMVar database, and confirmed the relationship between these identified mA-SNPs and their target genes in eQTL analysis and gene differential expression analysis. Finally, 26 genes corresponding to 20 mA-SNPs with eQTL signals were identified and differentially expressed (P < 0.05) in MS, 15 genes corresponding to 12 mA-SNPs (P < 1e-04) were differentially expressed in AD, and 27 PD-associated mA-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 mA-SNPs in disease pathogenesis as well as therapeutic target.